Publications by authors named "Javad Jamshidi"

39 Publications

Interleukine-22 gene variants are associated with susceptibility to visceral leishmaniasis.

Exp Parasitol 2021 Jun 8:108122. Epub 2021 Jun 8.

Department of Immunology, Fasa University of Medical Sciences, Fasa, Iran. Electronic address:

Visceral leishmaniasis (VL) is an infectious disease caused by an intracellular protozoan belonging to Leishmania species. Interleukin (IL)-22 plays an important role in inflammatory response, chemotaxis, regulation of cellular proliferation and tissue repair. Considering the role of IL-22 in control of leishmaniasis and the effect of its single nucleotide polymorphisms (SNPs) on respective function and production, this study aimed to investigate the probable association of IL-22 SNPs with VL. The study was carried out on 110 patients with VL, 102 healthy individuals with negative leishmanin skin test (negative control group (NCG)), and 144 healthy individuals with positive leishmanin skin test (LSTPG). Four SNPs in IL-22 including rs2227501, rs2227503, rs2227513 and rs1026786 were analyzed by polymerase chain reaction-restricted fragment length polymorphism (PCR- RFLP) in the study groups. The frequency of A allele and AA genotype at rs1026786 were significantly higher in the LSTPG group than in the patients (P = 0.013 and P = 0.001, respectively). Conversely, the frequency of AG genotype was significantly higher in the patients and the NCG than in the LSTPG group (P = 0.0001 and P = 0.002, respectively). For rs2227503, the frequency of AG genotype was significantly higher in the LSTPG group than in the NCG (P = 0.025). The haplotype TGAA frequency was significantly higher in the NCG, compared to patients and LSTPG group (P = 0.004 and P = 0.023, respectively). The frequencies of haplotypes TAAG and TGAG were significantly higher in the patients than in the LSTPG group (P = 0.046 and P = 0.014, respectively). The TAAA/TAAG frequency was significantly higher in the patients than in the LSTPG group (P = 0.013). Inheritance of rs1026786 A allele and AA genotype of IL-22 could be a possible protective factor against VL, whereas the inheritance of the haplotypes TAAG and TGAG may predispose Iranian population to the disease.
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http://dx.doi.org/10.1016/j.exppara.2021.108122DOI Listing
June 2021

LRP8 (rs5177) and CEP85L (rs11756438) are contributed to schizophrenia susceptibility in Iranian population.

Psychiatr Genet 2020 12;30(6):162-165

Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz.

Introduction Schizophrenia is recognized as one of the most important mental illnesses of the last century. Many genetic and environmental factors are involved in this condition. Recently, the genome-wide association study identified two significant genes LRP8 and CEP85L associated with psychiatric disorders. LRP8 (low-density lipoprotein receptor-related protein 8) acts as a cytoplasmic receptor for Reelin. Many studies have revealed that LRP8 was significantly related to schizophrenia and bipolar disorder in Chinese population. CEP85L standing for 'centrosomal protein 85 kDa-like' is another gene, which has been reportedly associated with BPD. Methods We performed a case-control study to analyze the association between rs5177 single-nucleotide polymorphism in the LRP8 gene plus the single-nucleotide polymorphism rs11756438 in the CEP85L gene and schizophrenia in the Iranian population. The genotype for rs5177 was determined by ARMS PCR method, while for rs11756438 genotype, it was determined by PCR-RFLP method after which statistical analysis was performed for each polymorphism. In rs5177, the CC genotype was susceptible to the disease while G allele was associated with disease protection. Results and Conclusion In rs11756438, the AA genotype was associated with disease susceptibility, while allele A did not have a significant association with the disease.
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http://dx.doi.org/10.1097/YPG.0000000000000266DOI Listing
December 2020

Diverse phenotypic measurements of wellbeing: Heritability, temporal stability and the variance explained by polygenic scores.

Genes Brain Behav 2020 11 9;19(8):e12694. Epub 2020 Sep 9.

Neuroscience Research Australia, Sydney, New South Wales, Australia.

Wellbeing, a key aspect of mental health, is moderately heritable with varying estimates reported from independent studies employing a variety of instruments. Recent genome-wide association studies (GWAS) have enabled the construction of polygenic scores (PGS) for wellbeing, providing the opportunity for direct comparisons of the variance explained by PGS for different instruments commonly employed in the field. Nine wellbeing measurements (multi-item and single-item), two personality domains (NEO-FFI neuroticism and extraversion), plus the depression domain of the DASS-42 were drawn from a larger self-report battery applied to the TWIN-E study-an Australian longitudinal twin cohort (N = 1660). Heritability was estimated using univariate twin modeling and 12-month test-retest reliability was estimated using intra-class correlation. PGS were constructed using wellbeing GWAS summary-statistics from Baselmans et al. (Nat Genet. 2019), and the variance explained estimated using linear models. Last, a GWAS was performed using COMPAS-W, a quantitative composite wellbeing measure, to explore its utility in genomic studies. Heritability estimates ranged from 23% to 47% across instruments, and multi-item measures showed higher heritability and test-retest reliability than single-item measures. The variance explained by PGS was ~0.5% to 1.5%, with considerable variation between measures, and within each measure over 12 months. Five loci with suggestive association (p < 1 × 10 ) were identified from this initial COMPAS-W wellbeing GWAS. This work highlights the variability across measures currently employed in wellbeing research, with multi-item and composite measures favored over single-item measures. While wellbeing PGS are useful in a research setting, they explain little of the phenotypic variance, highlighting gaps for improved gene discovery.
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http://dx.doi.org/10.1111/gbb.12694DOI Listing
November 2020

Electroencephalography profiles as a biomarker of wellbeing: A twin study.

J Psychiatr Res 2020 07 8;126:114-121. Epub 2020 May 8.

Neuroscience Research Australia, Randwick, New South Wales, 2031, Australia; School of Psychology, University of New South Wales, Sydney, New South Wales, 2052, Australia. Electronic address:

Alterations to electroencephalography (EEG) power have been reported for psychiatric conditions such as depression and anxiety, but not for mental wellbeing in a healthy population. This study examined the resting EEG profiles associated with mental wellbeing, and how genetics and environment contribute to these associations using twin modelling. Mental wellbeing was assessed using the COMPAS-W Wellbeing Scale which measures both subjective and psychological wellbeing. In 422 healthy adult monozygotic and dizygotic twins aged 18-61 years, we examined the association between mental wellbeing and EEG power (alpha, beta, theta, delta) using linear mixed models. This was followed by univariate and multivariate twin modelling to assess the heritability of wellbeing and EEG power, and whether the association was driven by shared genetics or environment. A significant association between wellbeing and an interaction of alpha, beta, and delta (ABD) power was found (β = -0.33, p < 0.001) whereby a profile of high alpha and delta and low beta was associated with higher wellbeing, independent of depression and anxiety symptoms. This finding was supported by a five-fold cross-validation analysis. A significant genetic correlation (rG = -0.43) was found to account for 94% of the association between wellbeing and the EEG power interaction. Together, this study has identified a novel EEG profile with a common genetic component that may be a potential biomarker of mental wellbeing. Future studies need to clarify the causal direction of this association.
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http://dx.doi.org/10.1016/j.jpsychires.2020.04.010DOI Listing
July 2020

Phenotypic and genotypic characterization of families with complex intellectual disability identified pathogenic genetic variations in known and novel disease genes.

Sci Rep 2020 01 22;10(1):968. Epub 2020 Jan 22.

Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.

Intellectual disability (ID), which presents itself during childhood, belongs to a group of neurodevelopmental disorders (NDDs) that are clinically widely heterogeneous and highly heritable, often being caused by single gene defects. Indeed, NDDs can be attributed to mutations at over 1000 loci, and all type of mutations, ranging from single nucleotide variations (SNVs) to large, complex copy number variations (CNVs), have been reported in patients with ID and other related NDDs. In this study, we recruited seven different recessive NDD families with comorbidities to perform a detailed clinical characterization and a complete genomic analysis that consisted of a combination of high throughput SNP-based genotyping and whole-genome sequencing (WGS). Different disease-associated loci and pathogenic gene mutations were identified in each family, including known (n = 4) and novel (n = 2) mutations in known genes (NAGLU, SLC5A2, POLR3B, VPS13A, SYN1, SPG11), and the identification of a novel disease gene (n = 1; NSL1). Functional analyses were additionally performed in a gene associated with autism-like symptoms and epileptic seizures for further proof of pathogenicity. Lastly, detailed genotype-phenotype correlations were carried out to assist with the diagnosis of prospective families and to determine genomic variation with clinical relevance. We concluded that the combination of linkage analyses and WGS to search for disease genes still remains a fruitful strategy for complex diseases with a variety of mutated genes and heterogeneous phenotypic manifestations, allowing for the identification of novel mutations, genes, and phenotypes, and leading to improvements in both diagnostic strategies and functional characterization of disease mechanisms.
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http://dx.doi.org/10.1038/s41598-020-57929-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976666PMC
January 2020

Homozygous Mutation in TWNK Cases Ataxia, Sensorineural Hearing Loss and Optic Nerve Atrophy.

Arch Iran Med 2019 12 1;22(12):728-730. Epub 2019 Dec 1.

Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.

The TWNK (C10orf2) gene encodes Twinkle, an essential helicase for mtDNA replication. Homozygous mutations in TWNK can lead to mitochondrial DNA depletion syndrome 7 (MTDPS7) that usually manifests as Infantile onset spinocerebellar ataxia (IOSCA). Here, we report a 15-year-old Iranian boy with three main symptoms; ataxia, sensorineural hearing loss and optic nerves atrophy which were accompanied by other symptoms including flexion contracture, dysarthric speech, nystagmus, dystonia and borderline intellectual disability. Whole exome sequencing (WES) revealed a homozygous mutation in his TWNK gene. The mutation was a transversion which replaced a C with A (NM_021830.4 (TWNK):c.874C>A). This nucleotide substitution results in replacing a Threonine with Proline in codon 292 of Twinkle protein (p.Pro292Thr). In silico analyses showed that this amino acid change in Twinkle could be deleterious and disease-causing; therefore, we attribute the symptoms of our patient to this mutation. Our study extended the homozygous mutation spectrum of the TWNK gene that leads to IOSCA.
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December 2019

Incomplete penetrance of gene for autosomal dominant form of cone-rod dystrophy.

Ophthalmic Genet 2019 06 19;40(3):259-266. Epub 2019 Jun 19.

b Ophthalmic Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran.

: Cone-rod dystrophy (CRD) is an inherited retinal dystrophy that is transmitted via different modes of inheritance. Mutations in more than 30 genes have been identified to cause the disease. We aimed to investigate the genetic agents of two unrelated cone-rod dystrophy affected Iranian families with autosomal recessive inheritance patterns. : Whole-exome sequencing (WES) was performed for identification of the disease-causing mutations in the probands of both families. The candidate mutations were further confirmed by Sanger sequencing. Samples from five available members of each family were then sequenced for the mutations present in the probands. Comprehensive ocular examinations for all members of the families carrying the mutations were completed by ophthalmologists. : We identified a novel premature stop codon c.310C>T in gene in heterozygote form in two symptomatic and two non-symptomatic members of one family (family-A), and a known mutation c.122G>A in homozygote form in another (family B). c.122G>A has been reported to cause late-onset autosomal dominant form of the disease in previous studies. However, the middle-aged heterozygous carriers of the mutation in this family showed normal phenotype. : The gene has been previously linked to the autosomal dominant form of cone-rod dystrophy. We report incomplete penetrance of gene for autosomal dominant form of the disease. Incomplete penetrance of the mutations may be partly caused by the influence of other genes in the complex genetic network underlying retinal regulation.
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http://dx.doi.org/10.1080/13816810.2019.1622023DOI Listing
June 2019

and rs35929607 polymorphisms and risk of Hypertension in Iranian Population.

Med J Islam Repub Iran 2018 20;32:14. Epub 2018 Feb 20.

Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.

ATP2B1 and STK39 have been introduced as essential hypertension candidate genes. The association of these genes' variations have not been studied in Iranian population yet. Here we aimed to investigate the association of ATP2B1 rs2681472 and STK39 rs35929607 polymorphisms with the risk of hypertension in an Iranian population. We included 400 individuals in our case-control study: 200 cases with essential hypertension and 200 healthy sex and age matched controls. All subjects were genotyped for rs2681472 and rs35929607 using a PCR-RFLP method. Genotype and allele frequencies were compared between the two groups using chi-squared test. The association was further assessed under log-additive, dominant and recessive genetic models. There was no association between rs2681472 and rs35929607 polymorphisms and risk of essential hypertension in our population (p>0.05). There was also no association between the studied polymorphisms and hypertension under different genetic models. Our study indicated that rs2681472 of ATP2B1 and rs35929607 of STK39 may not have a significant effect on the risk of essential hypertension in Iranian population. More studies are still needed to validate our results.
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http://dx.doi.org/10.14196/mjiri.32.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108259PMC
February 2018

Novel Mutations in Gene in Families with Gelatinous Drop-like Corneal Dystrophy (GDLD).

Int J Mol Cell Med 2017 11;6(4):204-211. Epub 2017 Dec 11.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

In the current study, we conducted a mutation screening of tumor-associated calcium signal transducer 2 () gene in six consanguineous Iranian families with gelatinous drop-like corneal dystrophy (GDLD), in order to find the causative mutations. Detailed eye examination was performed by ophthalmologist to confirm GDLD in patients. To detect the possible mutations, direct Sanger sequencing was performed for the only exon of gene, and its boundary regions in all patients. In the patients with GDLD, the corneal surface showed lesions with different shapes from mild to severe forms depending on the progress of the disease. The patients showed grayish corneal deposits as a typical mulberry form, corneal dystrophy along with corneal lipid deposition, and vascularization. Targeted Sanger sequencing in gene revealed the causative mutations in this gene in all studied families. Our study expanded the mutational spectrum of which along with the related symptoms could help with the diagnosis, and management of the disease.
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http://dx.doi.org/10.22088/BUMS.6.4.204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004293PMC
December 2017

A novel c.240_241insGG mutation in NDP gene in a family with Norrie disease.

Clin Exp Optom 2018 03 18;101(2):255-259. Epub 2017 Sep 18.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Norrie disease (ND) is a rare, X-linked recessive disorder with the main characteristic of early childhood blindness. The aim of the present study was to identify the genetic cause of the disease and the phenotypic characteristics of the patients in an Iranian family with four affected males with ND.

Methods: Norrie disease pseudoglioma (NDP) gene was sequenced and clinical examination was performed on patients.

Results: A GG dinucleotide insertion in exon 3 (c.240_241insGG) of NDP was detected in all patients. The mutation caused a frameshift and an early stop codon (p.Phe81Glyfs*23).

Conclusions: A novel mutation was found in the NDP gene in the affected males of the family. As the mutation was absent in the normal male members of the family, it should be the genetic cause of the disease.
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http://dx.doi.org/10.1111/cxo.12599DOI Listing
March 2018

A novel mutation in SMOC1 and variable phenotypic expression in two patients with Waardenburg anophthalmia syndrome.

Eur J Med Genet 2017 Nov 12;60(11):578-582. Epub 2017 Aug 12.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Waardenburg anophthalmia syndrome (WAS) is a rare disorder that mostly affects the eyes and distal limbs. In the current study we reported two Iranian patients with WAS. The first case was a 26-year-old girl with unilateral anophthalmia, bilateral camptodactyly and clinodactyly in her hands, oligodactly in her left foot and syndactyly of the second to fifth toes in her right foot. She also had severe hearing loss in both ears. The second case was a 12-year-old boy with bilateral anophthalmia, camptodactyly in his right hand, oligodactyly in his foot, clubfoot, and cryptorchidism. Both patients were mentally normal. To detect the causative mutation all exons and exon-intron boundaries of SMOC1 gene were sequenced in patients and other normal family members. We found a homozygous missense mutation (NM_001034852.2(SMOC1):c.367T > C) in exon 3 of SMOC1 gene in both patients. As the mutation segregated with the disease in the family, it should be the causative mutation. Our study extended the mutation spectrum of SMOC1 gene related to WAS.
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http://dx.doi.org/10.1016/j.ejmg.2017.08.006DOI Listing
November 2017

Support for "Disease-Only" Genotypes and Excess of Homozygosity at the CYTH4 Primate-Specific GTTT-Repeat in Schizophrenia.

Genet Test Mol Biomarkers 2017 Aug 19;21(8):485-490. Epub 2017 Jul 19.

10 Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences , Tehran, Iran .

Objective: The role of short tandem repeats (STRs) in the control of gene expression among species is being increasingly understood following the identification of several instances in which certain STRs occur identically, or expand differentially, in primates versus nonprimates. These STRs may regulate genes that participate in characteristics that are associated with the divergence of primates from sibling orders (e.g., brain higher order functions). The CYTH4 gene contains the longest tetranucleotide STR in its core promoter, at 7-repeats, and links to the evolution of human and nonhuman primates. Allele and genotype distribution of this STR were studied in patients affected by schizophrenia (SCZ) and controls.

Methods: High-resolution data were obtained on the allele and genotype distribution of the CYTH4 STR and a novel C > T single-nucleotide polymorphism (SNP) at its immediate upstream sequence in 255 patients with SCZ and 249 controls. Each sample was sequenced twice using the fluorescent dye termination method.

Results: Novel alleles were detected at the long extreme of the GTTT-repeat, at 10- and 11-repeats, in the SCZ cases and controls. Excess of homozygosity was observed for the entire range of alleles across the GTTT-repeat and the C > T SNP in the SCZ patients in comparison with the controls (Yates corrected p < 0.011). Three genotypes consisting of the 11-repeat allele (i.e., 11/11, 10/11, and 7/11) were detected only in the SCZ patients (i.e., disease-only genotypes), and contributed to 2.3% of the SCZ genotypes (Mid p exact <0.007). The frequency of the 11-repeat allele was estimated at 0.02 and 0.006 in the SCZ patients and controls, respectively (Mid p exact <0.006).

Conclusion: This indicates that STR genotypes that are absent in the control group may be risk factors for SCZ. Future studies are warranted to test the significance of our findings.
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http://dx.doi.org/10.1089/gtmb.2016.0422DOI Listing
August 2017

Association of renin-angiotensin-aldosterone system gene polymorphisms with left ventricular hypertrophy in patients with heart failure with preserved ejection fraction: A case-control study.

Clin Exp Hypertens 2017 17;39(4):371-376. Epub 2017 May 17.

a Noncommunicable Diseases Research Center , Fasa University of Medical Sciences , Fasa , Iran.

Background: Heart failure with preserved ejection fraction (HFpEF) has close ties with hypertension, though risk factors to the development of HFpEF in hypertensive patients are not fully understood. Left ventricular hypertrophy (LVH) signifies the susceptibility toward diastolic heart dysfunction, and genetic determinants of LVH as a result may serve as risk predictors for HFpEF in hypertension. We investigated the role of three renin-angiotensin-aldosterone system (RAAS) gene polymorphisms in the development of LVH in hypertensive patients with a diagnosis of HFpEF.

Methods: A total of 176 hypertensive patients with a diagnosis of HFpEF were divided to cases with LVH and controls without. rs4343 and rs4291 of angiotensin-converting enzyme (ACE) and rs5186 of angiotensin receptor type 1 were genotyped using PCR-RFLP method.

Results: Genotypes and allele frequencies were significantly different between the case and control groups for rs4343 and rs4291, whereas no difference was observed for rs5186.

Conclusion: Increased ACE activity explains the significant association of rs4343 and rs4291 polymorphisms with LVH in the carriers. Furthermore, findings support the pathophysiologic links between RAAS and increased LV mass in hypertension and suggest a genetic susceptibility to HFpEF. Such polymorphisms may serve as risk predictors of HFpEF in hypertensive patients.
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http://dx.doi.org/10.1080/10641963.2016.1267196DOI Listing
February 2018

A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive Parkinsonism Revealed Known and Novel Gene Mutations.

Mol Neurobiol 2018 Apr 13;55(4):3477-3489. Epub 2017 May 13.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.
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http://dx.doi.org/10.1007/s12035-017-0535-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683945PMC
April 2018

Association of β-Secretase Functional Polymorphism with Risk of Schizophrenia.

Genet Test Mol Biomarkers 2017 Apr 21;21(4):248-251. Epub 2017 Feb 21.

1 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran .

Aim: The NRG1-ERBB4 neurotransmitter signaling pathway plays a key role in the pathogenesis of schizophrenia (SZ). The intronic single-nucleotide polymorphism rs707284 in ERBB4 links to PI3K-AKT suppression in SZ. Another protein indirectly affecting NRG1-ERBB4 signaling is β-secretase, which is encoded by the BACE1 gene, and activates NRG1 by proteolytic cleavage. In this study, we aimed to investigate the association of ERBB4 rs707284 and BACE1 rs490460 with the risk of SZ in an Iranian population.

Subjects And Methods: A total of 973 subjects, including 480 SZ patients and 493 healthy controls, matched by ethnicity, age, and gender, were recruited in a case-control study. Genomic DNA was extracted from peripheral blood of all subjects and genotyping of rs707284 and rs490460 was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and tetra-primer amplification refractory mutation system (tetra-ARMS) PCR genotyping assays, respectively.

Results: A significant association was observed between the rs490460 T allele and SZ (p = 0.0002, odds ratio 0.69, 95% confidence interval 0.57-0.84). There was no association between the risk of SZ and rs707284.

Conclusion: Our data indicate that rs490460 is associated with the risk of SZ. In silico analysis indicates that rs490460 may be a potential splicing site, which affects protein structure. Replication studies are needed to confirm our data.
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http://dx.doi.org/10.1089/gtmb.2016.0262DOI Listing
April 2017

Analysis of Copy Number Variations in Patients with Autism Using Cytogenetic and MLPA Techniques: Report of 16p13.1p13.3 and 10q26.3 Duplications.

Int J Mol Cell Med 2016 5;5(4):236-245. Epub 2016 Dec 5.

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

Autism is a common neuropsychiatric disorder affecting 1 in 68 children. Copy number variations (CNVs) are known to be major contributors of autism spectrum disorder (ASD). There are different whole genome or targeted techniques to identify CNVs in the patients including karyotyping, multiplex ligation-dependent probe amplification (MLPA) and array CGH. In this study, we used karyotyping and MLPA to detect CNVs in 50 Iranian patients with autism. GTG banding and 4 different MLPA kits (2 subtelomeric and 2 autism kits) were utilized. To elevate our detection rate, we selected the sporadic patients who had additional clinical features including intellectual disability, seizure, attention deficit hyperactivity disorder, and abnormal head circumference. Two out of 50 patients (4%) showed microscopic chromosome abnormalities and 5 out of 50 (10%) demonstrated copy number gains or losses using MLPA kits. Including one overlapping result between karyotype and MLPA techniques, our overall detection rate was 6 out of 50 (12%). Three out of 6 CNVs were de novo and three others were paternally inherited. Two of CNVs detected by karyotyping and MLPA tests were 16p13.1q13.3 and 10q26.3 duplications, respectively. For these two CNVs genotype and phenotype of the patients were compared with other studies. Although the pathogenicity of cytogenetic results was certain, most of MLPA results needed to be better refined using other more accurate techniques such as array CGH. Our findings suggest that it might be possible to obtain some useful information using MLPA technique but it cannot be used as a single diagnostic tool for the autism.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353985PMC
December 2016

Omentin Val109Asp polymorphism and risk of coronary artery disease.

Asian Cardiovasc Thorac Ann 2017 Mar 8;25(3):199-203. Epub 2017 Mar 8.

5 Department of Cardiology, Fasa University of Medical Sciences, Fasa, Iran.

Background Omentin is an adipocytokine with antiinflammatory properties. It has been reported to be involved in atherosclerosis and coronary artery disease. We aimed to investigate the association of omentin Val109Asp polymorphism with coronary artery disease in an Iranian population. Methods For a case-control study, 400 individuals were recruited: 200 with coronary artery disease and 200 healthy controls. Patients with coronary artery disease were diagnosed by angiography as having at least one main coronary artery with more than 50% stenosis. Genotyping of Val109Asp was carried out using a polymerase chain reaction DNA-restriction fragment length polymorphism technique. Results There was no association between Val109Asp polymorphism and the risk of coronary artery disease in our study population ( p = 0.20). However, when subgroup analysis was performed according to sex, there was a significant difference in the distribution of alleles between groups for men ( p = 0.031, odds ratio = 0.57, 95% confidence interval: 0.35-0.95) but not for women ( p = 0.88, odds ratio = 1.03, 95% confidence interval: 0.66-1.61). Conclusions Our results indicate that the Asp allele of Val109Asp (T allele of rs2274907) is more frequent among men with coronary artery disease than healthy men, so it is possibly a risk factor for coronary artery disease in men only. The difference in association between men and women may be due to the different distribution and metabolism of adipose tissue in men and women. More studies with larger sample sizes and in different populations are required to validate our study results.
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http://dx.doi.org/10.1177/0218492317699752DOI Listing
March 2017

RAB7L1 promoter polymorphism and risk of Parkinson's disease; a case-control study.

Neurol Res 2017 May 28;39(5):468-471. Epub 2017 Feb 28.

f Faculty of Medicine, Department of Medical Genetics , Tabriz University of Medical Sciences , Tabriz , Iran.

Introduction: Recent genome-wide association studies have explored some new loci in association with Parkinson's disease (PD). RAB7L1 is an important gene involved in one of the important neurological pathways, located in PARK16 locus. We performed a case-control study to examine the association between rs823144 SNP located in the promoter region of the RAB7L1 gene and PD risk in Iranian population.

Methods: A total of 960 samples including 480 PD patients and 480 healthy controls were collected for analysis of the RAB7L1 rs823144 polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR - RFLP) method.

Results: We found significant differences in genotypic and allelic frequencies between patients and controls. Significant association was found between presence of minor allele (C) and decreased risk of PD development (p = 0.008, OR = 0.74 (0.605-0.924)). Also another significant association was observed between the CC genotype and PD (p = 0.004, OR = 0.441 (0.252-0.772)).

Conclusion: Our data support the association between rs823144 and decreased risk of PD.
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http://dx.doi.org/10.1080/01616412.2017.1297558DOI Listing
May 2017

Emery-Dreifuss Muscular Dystrophy: a Report of a Large Family with 11 Affected Individuals.

Int J Mol Cell Med 2016 4;5(3):196-198. Epub 2016 Sep 4.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125372PMC
September 2016

Copy Number Variants in Patients with Autism and Additional Clinical Features: Report of VIPR2 Duplication and a Novel Microduplication Syndrome.

Mol Neurobiol 2017 11 28;54(9):7019-7027. Epub 2016 Oct 28.

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

Autism is a common neurodevelopmental disorder estimated to affect 1 in 68 children. Many studies have shown the role of copy number variants (CNVs) as a major contributor in the etiology of autism with the overall detection rate of about 10-15 % and over 20 % when syndromic forms of autism exist. In this study, we used array CGH to identify CNVs in 15 Iranian patients with autism. To elevate our diagnostic yield, we selected the sporadic patients who had additional clinical features including intellectual disability (ID), craniofacial anomaly, and seizure. Six out of 15 patients showed clinically relevant CNVs including pathogenic and likely pathogenic copy number gains or losses. We report a novel gene duplication syndrome (10q21.2q21.3 microduplication) and present a new evidence for VIPR2 duplication, as a candidate gene for autism. Furthermore, we describe the first manifesting carrier female with deletion of SLC6A8 and BCAP31 genes on Xq28. Our findings suggest that there might be a higher prevalence of clinically significant CNVs in patients with autism and additional clinical manifestations. The CNV analysis in such patients could lead to the discovery of novel syndromes as well as unraveling the etiology of autism.
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http://dx.doi.org/10.1007/s12035-016-0202-yDOI Listing
November 2017

A genetic variant in miRNA binding site of glutamate receptor 4, metabotropic (GRM4) is associated with increased risk of major depressive disorder.

J Affect Disord 2017 01 17;208:218-222. Epub 2016 Oct 17.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Glutamate receptor 4, metabotropic (GRM4) expression is increased in the brain of patients with depression. The poorly conserved miR-1202 is downregulated in depression and is negatively correlated with GRM4. A variation located at the 3' UTR of the GRM4 gene may influence the interaction between miR-1202 and GRM4. The aim of this study was to determine the possible association between GRM4 3' UTR variant (rs2229901) and major depressive disorder (MDD).

Methods: A total of 500 subjects comprising 250 patients with MDD and 250 healthy controls were included in our study. The single nucleotide polymorphism rs2229901 was genotyped using PCR-RFLP method. Allele and genotype frequencies were compared between the two groups using chi-square test and logistic regression models. The impact of rs2229901 on GRM4/miR-1202 hybrid stability and local GRM4-3' UTR secondary structure were assessed using RNAsnp program.

Results: Genotype and allele frequency of rs2229901were significantly different in patients with MDD comparing to the control group (p=0.018 and p=0.007, respectively). The G-allele was more prevalent among patients with MDD. The rs2229901 variant was predicted to be structure-disruptive.

Limitations: The relatively small sample size and lack of functional experiments are the major limitations of this study.

Conclusion: Our results suggest that rs2229901 is associated with MDD risk. This variant probably impacts the interaction between GRM4 and miR-1202. Functional studies are needed to clarify the possible mechanisms by which rs2229901 influences MDD risk.
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http://dx.doi.org/10.1016/j.jad.2016.10.008DOI Listing
January 2017

SNAP-25 gene variations and attention-deficit hyperactivity disorder in Iranian population.

Neurol Res 2016 Nov 15;38(11):959-964. Epub 2016 Sep 15.

f Department of Medical Genetics , School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran , Iran.

Objectives: Attention deficit hyperactivity disorder (ADHD) is a common psychiatric condition of childhood characterized by persistent symptoms of hyperactivity, inattention, and impulsivity. The objective of this study was to investigate the association of synaptosomal-associated protein of 25 kDa (SNAP-25) gene variants with ADHD.

Methods: A case-control study with a total of 150 children with ADHD (mean age 9.61; range 6-16; gender ratio 105m/45f) and 150 normal children (mean age 10.02; range 6-16; gender ratio 98m/52f) was conducted. Genomic DNA was extracted from peripheral blood of all samples and SNPs rs78428954 and rs3746544 located in SNAP-25 gene were genotyped.

Results: Our analysis indicated that there is no significant association between none of studied variants in SNAP-25 and ADHD.

Discussion: To our knowledge, it is the first report of SNAP-25 genotyping in Iranian patients with ADHD. Further investigations with larger populations are needed in order to clarify the exact role of SNAP-25 variations in susceptibility to ADHD.
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http://dx.doi.org/10.1080/01616412.2016.1232548DOI Listing
November 2016

A cohort study protocol to analyze the predisposing factors to common chronic non-communicable diseases in rural areas: Fasa Cohort Study.

BMC Public Health 2016 10 18;16(1):1090. Epub 2016 Oct 18.

Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Non-communicable diseases (NCDs) have become the main causes of morbidity and mortality even in rural areas of many developing countries, including Iran. In view of this increased risk, Fasa Cohort Study (FACS) has been established to assess the risk factors for NCDs with the ultimate goal of providing optimal risk calculators for Iranian population and finding grounds for interventions at the population level.

Methods: In a population-based cohort, at least 10,000 people within the age range of 35 to 70 years old from Sheshdeh, the suburb of Fasa city and its 24 satellite villages are being recruited. A detailed demographic, socioeconomic, anthropometric, nutrition, and medical history is obtained for each individual besides limited physical examinations and determination of physical activity and sleep patterns supplemented by body composition and electrocardiographic records. Routine laboratory assessments are done and a comprehensive biobank is compiled for future biological investigations. All data are stored online using a dedicated software.

Discussion: FACS enrolls the individuals from rural and little township areas to evaluate the health conditions and analyze the risk factors pertinent to major NCDs. This study will provide an evidence-based background for further national and international policies in preventive medicine. Yearly follow ups are designed to assess the health events in the participating population. It is believed that the results would construct a contemporary knowledge of Iranian high risk health characteristics and behaviors as well as the platform for further interventions of risk reduction in a typical Iranian population. Constantly probing for future advances in NCDs prevention and management, the accumulated database and biobank serves as a potential for state of the art research and international collaborations.
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http://dx.doi.org/10.1186/s12889-016-3760-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069851PMC
October 2016

PTRHD1 (C2orf79) mutations lead to autosomal-recessive intellectual disability and parkinsonism.

Mov Disord 2017 02 18;32(2):287-291. Epub 2016 Oct 18.

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Introduction: Atypical parkinsonism is a neurodegenerative disease that includes diverse neurological and psychiatric manifestations.

Objectives: We aimed to identify the disease-cauisng mutations in a consanguineous family featuring intellectual disability and parkinsonism.

Methods: Full phenotypic characterization, followed by genome-wide single-nucleotide polymorphism genotyping and whole-genome sequencing, was carried out in all available family members.

Results: The chromosome, 2p23.3, was identified as the disease-associated locus, and a homozygous PTRHD1 mutation (c.157C>T) was then established as the disease-causing mutation. The pathogenicity of this PTRHD1 mutation was supported by its segregation with the disease status, its location in a functional domain of the encoding protein, as well as its absence in public databases and ethnicity-matched control chromosomes.

Conclusion: Given the role of 2p23 locus in patients with intellectual disability and the previously reported PTRHD1 mutation (c.155G>A) in patients with parkinsonism and cognitive dysfunction, we concluded that the PTRHD1 mutation identified in this study is likely to be responsible for the phenotypic features of the family under consideration. © 2016 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.26824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318269PMC
February 2017

Genetic Analysis of the ZNF512B, SLC41A1, and ALDH2 Polymorphisms in Parkinson's Disease in the Iranian Population.

Genet Test Mol Biomarkers 2016 Oct 9;20(10):629-632. Epub 2016 Sep 9.

5 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran .

Aims: Parkinson's disease (PD) is one of the most common neurodegenerative disorders; its etiology includes both genetic and environmental factors and their interactions. The ZNF512B, SLC41A1, and ALDH2 genes have recently been identified as contributing to PD. In this study we investigated the association of alleles of these genes with PD in the Iranian population.

Methods: In a case-control study, rs2275294, rs11240569, and rs4767944, three single nucleotide polymorphisms in ZNF512B, SLC41A1, and ALDH2 genes, respectively, were genotyped in 490 PD patients and 490 controls. The genotype and allele frequencies were compared between the two groups using chi-square and logistic regression tests.

Results: A significant association between the rs11240569 polymorphism and a reduced risk of PD was found (p = 0.014, OR = 0.76, 95% CI: 0.60-0.94 for allele frequencies). We did not find any associations between PD and the rs2275294 and rs4767944 polymorphisms.

Conclusion: The association of rs11240569 polymorphism in SLC41A1 gene with reduced risk of PD was replicated in our population.
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http://dx.doi.org/10.1089/gtmb.2016.0133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871989PMC
October 2016

SIPA1L2, MIR4697, GCH1 and VPS13C loci and risk of Parkinson's diseases in Iranian population: A case-control study.

J Neurol Sci 2016 Oct 2;369:1-4. Epub 2016 Aug 2.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Prevalence of PD increases steadily with age. A recent meta-analysis of genome-wide association studies has identified six new loci to be linked with PD. Here we investigated the association of four of these new loci, SIPA1L2, MIR4697, GCH1 and VPS13C with PD in an Iranian population. Through a case-control study a total of 1800 subjects comprising 600 PD patients and 1200 unrelated healthy controls were recruited. Rs10797576, rs329648, rs11158026 and rs2414739 related to SIPA1L2, MIR4697, GCH1 and VPS13C loci respectively, were genotyped in all subjects. The difference of genotype and allele frequencies between case and control groups were investigated using chi-square test and logistic regression models with R software. Genotype and allele frequencies were significantly different in PD patients and control group for rs329648, rs11158026 and rs2414739 (p-value=0.018, 0.025, and 0.009 respectively for allele frequency differences). There was no difference in genotype nor allele frequencies between the two groups for rs10797576. We replicated the association of three new loci which are proposed for PD. More studies in other populations and also functional analysis are required to clear the role of these variants in PD.
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http://dx.doi.org/10.1016/j.jns.2016.08.001DOI Listing
October 2016

Bioinformatic tools to determine the pathogenicity of a missense mutation in PKHD1 in autosomal recessive polycystic kidney disease.

Nephrology (Carlton) 2017 04;22(4):330-331

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.1111/nep.12919DOI Listing
April 2017

A Novel PKD1 Mutation in a Patient with Autosomal Dominant Polycystic Kidney Disease.

Int J Mol Cell Med 2016 8;5(2):123-4. Epub 2016 Jun 8.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947217PMC
August 2016

Analysis of CYP17, CYP19 and CYP1A1 Gene Polymorphisms in Iranian Women with Breast Cancer.

Asian Pac J Cancer Prev 2016 ;17(S3):23-6

Infertility and Reproductive Health Research Centre (IRHRC), School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran E-mail:

Breast cancer (BC) is the most common cancer and the second cause of mortality in women all around the world. It is caused by several factors including genetic determinants, so that both genetic susceptibility factors and environmental factors are involved in the etiology. Significance of genes functioning in steroid hormone synthesis and metabolism are well established in breast cancer susceptibility. In this study, 134 women with BC and 135 normal controls were analyzed for their genotypes for the polymorphisms, rs743572, rs10046 and rs4646903, resided in CYP17, CYP19 and CYP1A1 genes, respectively. Significant differences in distributions of allele and genotype frequencies were found for the rs10046 polymorphism in CYP19 (p-value=0.01, OR (CI 95%) =1.59 (1.1-2.3), p-value=0.04, OR (CI 95%) =1.7 (1.1-2.5) respectively). For rs743,572 and rs 4646903 polymorphisms, no significant associations were observed. A significant association was observed between the rs10046 polymorphism of the CYP19gene and breast cancer in Iranian patients. Due to inconsistent previous results, more studies in different populations with larger sample sizes are indicated.
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http://dx.doi.org/10.7314/apjcp.2016.17.s3.23DOI Listing
February 2017

RIT2 Polymorphisms: Is There a Differential Association?

Mol Neurobiol 2017 04 3;54(3):2234-2240. Epub 2016 Mar 3.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Neurological disorders include a wide variety of mostly multifactorial diseases related to the development, survival, and function of the neuron cells. Single-nucleotide polymorphisms (SNPs) have been extensively studied in neurological disorders, and in a number of instances have been reproducibly linked to disease as risk factors. The RIT2 gene has been recently shown to be associated with a number of neurological disorders, such as Parkinson's disease (PD) and autism. In the study reported here, we investigated the association of the rs12456492 and rs16976358 SNPs of the RIT2 gene with PD, essential tremor (ET), autism, schizophrenia (SCZ), and bipolar disorder (BPD; total of 2290 patients), and 1000 controls, by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Significant association was observed between rs12456492 and two disorders, PD and ET, whereas rs16976358 was found to be associated with autism, SCZ, and BPD. Our findings are indicative of differential association between the RIT2 SNPs and different neurological disorders.
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http://dx.doi.org/10.1007/s12035-016-9815-4DOI Listing
April 2017