Publications by authors named "Nayereh Nouri"

21 Publications

  • Page 1 of 1

Autozygosity-driven genetic diagnosis in consanguineous families from Italy and the Greater Middle East.

Hum Genet 2020 Nov 2;139(11):1429-1441. Epub 2020 Jun 2.

Medical Genetics Sant'Orsola, Malpighi University Hospital of Bologna, Via Massarenti 9, 40138, Bologna, Italy.

Autozygosity-driven exome analysis has been shown effective for identification of genes underlying recessive diseases especially in countries of the so-called Greater Middle East (GME), where high consanguinity unravels the phenotypic effects of recessive alleles and large family sizes facilitate homozygosity mapping. In Italy, as in most European countries, consanguinity is estimated low. Nonetheless, consanguineous Italian families are not uncommon in publications of genetic findings and are often key to new associations of genes with rare diseases. We collected 52 patients from 47 consanguineous families with suspected recessive diseases, 29 originated in GME countries and 18 of Italian descent. We performed autozygosity-driven exome analysis by detecting long runs of homozygosity (ROHs > 1.5 Mb) and by prioritizing candidate clinical variants within. We identified a pathogenic synonymous variant that had been previously missed in NARS2 and we increased an initial high diagnostic rate (47%) to 55% by matchmaking our candidate genes and including in the analysis shorter ROHs that may also happen to be autozygous. GME and Italian families contributed to diagnostic yield comparably. We found no significant difference either in the extension of the autozygous genome, or in the distribution of candidate clinical variants between GME and Italian families, while we showed that the average autozygous genome was larger and the mean number of candidate clinical variants was significantly higher (p = 0.003) in mutation-positive than in mutation-negative individuals, suggesting that these features influence the likelihood that the disease is autozygosity-related. We highlight the utility of autozygosity-driven genomic analysis also in countries and/or communities, where consanguinity is not widespread cultural tradition.
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http://dx.doi.org/10.1007/s00439-020-02187-7DOI Listing
November 2020

ROCK1 is associated with non-syndromic cleft palate.

J Oral Pathol Med 2020 Feb 24;49(2):164-168. Epub 2019 Nov 24.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Background: Craniofacial morphogenesis is the result of an intricate multistep network of tightly controlled spatial and temporal signalling that involves several molecules and transcription factors organized into highly coordinated pathways. Any alteration in even one step of this delicate process can lead to congenital malformations such as cleft palate. One of the first steps in embryonal orofacial development is the migration of cells from the neural crests to the branchial arches. Next, the cells have to proliferate, differentiate, move and connect to each other in order to correctly form the palate. Cell contraction, promoted by the interaction of non-muscle myosin II and actin A, is a crucial step in morphogenesis and is regulated by ROCK1 protein.

Methods: A family-based association study was carried out in order to verify whether or not genetic variants of ROCK1 were associated with non-syndromic cleft palate (nsCP). Two cohorts from Italy and Iran, a total of 189 nsCP cases and their parents were enrolled.

Results: The rs35996865-G allele was under-transmitted in cases of nsCP [P = .006, odds ratio (OR) = 0.63 (95% CI 0.45-0.88)].

Conclusion: This investigation reveals for the first time data supporting a role for ROCK1 in nsCP aetiology.
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http://dx.doi.org/10.1111/jop.12973DOI Listing
February 2020

Non-syndromic cleft palate: Association analysis on three gene polymorphisms of the folate pathway in Asian and Italian populations.

Int J Immunopathol Pharmacol 2019 Jan-Dec;33:2058738419858572

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Periconceptional folic acid supplementation can reduce the risk of inborn malformations, including orofacial clefts. Polymorphisms of MTHFR, TCN2, and CBS folate-related genes seem to modulate the risk of cleft lip with or without cleft palate (CL/P) in some populations. CL/P and cleft palate only (CPO) are different malformations that share several features and possibly etiological causes. In the present investigation, we conducted a family-based, candidate gene association study of non-syndromic CPO. Three single nucleotide polymorphisms, namely, rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were investigated in a sample that included 129 Italian and 65 Asian families. No evidence of association between the three genotyped polymorphisms and CPO was found in the Italian and Asian cases, indeed the transmission disequilibrium test did not detect any asymmetry of transmission of alleles. This investigation, although with some limitation, further supports that CL/P and CPO diverge in their genetic background.
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http://dx.doi.org/10.1177/2058738419858572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822179PMC
March 2020

Consanguineous marriages in the genetic counseling centers of Isfahan and the ethical issues of clinical consultations.

J Med Ethics Hist Med 2017 10;10:12. Epub 2017 Dec 10.

Professor, Medical Ethics and History of Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Consanguineous marriage, which is common in many regions in the world, has absorbed much attention as a causative factor in raising the incidence of genetic diseases. The adverse effects may be attributed to the expression of the genes received from common ancestors and mortality and morbidity of the offspring. Iran has a high rate of consanguineous marriages. In recent years genetic counseling has come to be considered in health care services. This cross-sectional study was conducted in order to determine the prevalence and types of consanguineous marriages in the genetic clinics in Isfahan. We aimed to define the different types of marriages, specific categories of genetic disorders associated with consanguineous marriages, and mode of inheritance in the family tree. We also narratively reviewed the ethical aspects of the issue. The data were collected using a simple questionnaire. A total number of 1535 couples from urban and rural areas formed the study population. The marriages were classified according to the degree of the relationship between couples, including: double cousin, first cousin, first cousin once removed, second cousin and beyond second cousin. The SPSS software version 16 was used for data analysis. Data obtained through genetic counseling offered during a 5-year period revealed that 74.3% had consanguineous relationships, 62.3% were first cousins, 1% were double cousins and 7.8% were second cousins. In addition, 76% of the couples had at least one genetic disease in their family tree. Related ethical issues were also considered in this study, including autonomy and informed decision making, benefit and harm assessment, confidentiality, ethics in research, justice in access to counseling services, financial problems ethics, and the intellectual property of scientific success.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797678PMC
December 2017

Possible effect of SNAIL family transcriptional repressor 1 polymorphisms in non-syndromic cleft lip with or without cleft palate.

Clin Oral Investig 2018 Sep 27;22(7):2535-2541. Epub 2018 Jan 27.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Belmeloro, 8, 40126, Bologna, Italy.

Objective: Orofacial development is a complex process subjected to failure impairing. Indeed, the cleft of the lip and/or of the palate is among the most frequent inborn malformations. The JARID2 gene has been suggested to be involved in non-syndromic cleft lip with or without cleft palate (nsCL/P) etiology. JARID2 interacts with the polycomb repressive complex 2 (PRC2) in regulating the expression patterns of developmental genes by modifying the chromatin state.

Materials And Methods: Genes coding for the PRC2 components, as well as other genes active in cell differentiation and embryonic development, were selected for a family-based association study to verify their involvement in nsCL/P. A total of 632 families from Italy and Asia participated to the study.

Results: Evidence of allelic association was found with polymorphisms of SNAI1; in particular, the rs16995010-G allele was undertransmitted to the nsCL/P cases [P = 0.004, odds ratio = 0.69 (95% C.I. 0.54-0.89)]. However, the adjusted significance value corrected for all the performed tests was P = 0.051.

Conclusions: The findings emerging by the present study suggest for the first time an involvement of SNAI1 in the nsCL/P onset.

Clinical Relevance: Interestingly, SNAI1 is known to promote epithelial to mesenchymal transition by repressing E-cadherin expression, but it needs an intact PRC2 to act this function. Alterations of this process could contribute to the complex etiology of nsCL/P.
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http://dx.doi.org/10.1007/s00784-018-2350-0DOI Listing
September 2018

Prevalence of 22q11.2 microdeletion syndrome in Iranian patients with cleft palate.

Adv Biomed Res 2016 27;5:201. Epub 2016 Dec 27.

Isfahan Cleft Lip and Palate Clinic, Faculty of Rehabilitation, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Surgery, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: 22q11.2 microdeletion syndrome is the most common multiple genetic disorder associated with learning disabilities, developmental delays, immune deficiency, hypocalcemia, and cleft palate. Finding some valid criteria for screening of 22q11.2 deletion syndromes in infants would be very helpful in early diagnosis and treatment.

Materials And Methods: Since 69% of individuals with 22q11.2 deletion have a palatal abnormality, we studied the prevalence of 22q11.2 deletion syndrome in 378 Iranian patients during a 5-year period, including 291 patients affected with cleft palate only without cleft lip (CPO) and 87 patients affected with velopharyngeal incompetence (VPI) and/or submucous cleft palate (SMCP). DNA copy number was analyzed with multiplex ligation-dependent probe amplification (MLPA) technique.

Results: In our study, 15/378 (3.97%) patients with palatal anomalies showed 22q11.2 deletion. Interestingly, this prevalence between syndromic patients was 15/104 (14.42%).

Conclusion: It seems that SMCP or VPI, in addition to one or more another features of 22q11.2 deletions, especially developmental delay, may be good criteria for molecular investigation of 22q11.2 region.
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http://dx.doi.org/10.4103/2277-9175.192728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220684PMC
December 2016

Reciprocal 22q11.2 Deletion and Duplication in Siblings with Karyotypically Normal Parents.

Cytogenet Genome Res 2016 8;148(1):1-5. Epub 2016 Apr 8.

Laboratory for Cytogenetics and Genome Research, Center of Human Genetics, KU Leuven, Leuven, Belgium.

The 22q11.2 locus is known to harbor a high risk for structural variation caused by non-allelic homologous recombination, resulting in deletions and duplications. Here, we describe the first family with one sibling carrying the 22q11 deletion and the other carrying the reciprocal duplication. FISH and SNP array analysis of the parents show a maternal origin for both deletion and duplication, without indications of balanced deletions/duplications or mosaicism. We hypothesize that germline mosaicism in the mother underlies the deletion and duplication, which would implicate a high recurrence risk for her offspring.
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http://dx.doi.org/10.1159/000445089DOI Listing
January 2017

Identification of Proximal and Distal 22q11.2 Microduplications among Patients with Cleft Lip and/or Palate: A Novel Inherited Atypical 0.6 Mb Duplication.

Genet Res Int 2015 12;2015:398063. Epub 2015 Nov 12.

Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran ; Craniofacial and Cleft Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Misalignments of low-copy repeats (LCRs) located in chromosome 22, particularly band 22q11.2, predispose to rearrangements. A variety of phenotypic features are associated with 22q11.2 microduplication syndrome which makes it challenging for the genetic counselors to recommend appropriate genetic assessment and counseling for the patients. In this study, multiplex ligation probe dependent amplification (MLPA) analysis was performed on 378 patients with cleft lip and/or palate to characterize rearrangements in patients suspected of 22q11.2 microduplication and microdeletion syndromes. Of 378 cases, 15 were diagnosed with a microdeletion with various sizes and 3 with duplications. For the first time in this study an atypical 0.6 Mb duplication is reported. Illustration of the phenotypes associated with the microduplications increases the knowledge of phenotypes reported in the literature.
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http://dx.doi.org/10.1155/2015/398063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660028PMC
December 2015

Non-syndromic cleft lip with or without cleft palate in Asian populations: Association analysis on three gene polymorphisms of the folate pathway.

Arch Oral Biol 2016 Jan 27;61:79-82. Epub 2015 Oct 27.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Belmeloro, 8, 40126 Bologna, Italy.

Objective: Orofacial clefts (OFCs) are one of the most common birth defects in humans. They are the subject of a number of investigations aimed at elucidating the bases of their complex mode of inheritance involving both genetic and environmental factors. Genes belonging to the folate pathway have been among the most studied. The aim of the investigation was to replicate previous studies reporting evidence of association between polymorphisms of folate related genes and the occurrence of non-syndromic cleft lip with or without cleft palate (NSCL/P), using three independent samples of different ancestry: from Tibet, Bangladesh and Iran, respectively.

Design: Specifically, the polymorphisms rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were tested.

Results: A decreased risk of NSCL/P was observed in patients presenting the C677T variant at MTHFR gene (relative risk for heterozygotes=0.53; 95% confidence interval [C.I.]=0.32-0.87). The investigated polymorphisms mapping at TCN2 and CBS genes did not provide any evidence of association.

Conclusion: Overall, these results indicate that NSCL/P risk factors differ among populations and confirm the importance of testing putative susceptibility variants in different genetic backgrounds.
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http://dx.doi.org/10.1016/j.archoralbio.2015.10.019DOI Listing
January 2016

Family-based association analysis between nonsyndromic cleft lip with or without cleft palate and IRF6 polymorphism in an Iranian population.

Clin Oral Investig 2015 May 16;19(4):891-4. Epub 2014 Sep 16.

Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.

Objectives: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect which is strongly associated with genetic factors. Previous studies in several populations showed a significant correlation between IRF6 rs642961 polymorphism and NSCL/P. The aim of this study is to indicate the correlation of IRF6 rs642961 polymorphism and NSCL/P in Iranian NSCL/P families.

Material And Methods: In this study, we analyzed IRF6 rs642961 genotype in 352 individuals from 102 Iranian nuclear families affected by NSCL/P using iPlex assay on a Sequenom MassARRAY platform. Hardy-Weinberg equilibrium and Mendelian error checking were performed by Haploview 4.2. Allelic association analysis was conducted with family-based association tests implemented in FBAT program v2.03.

Results: The family-based association analysis revealed no significant association between IRF6 rs642961 genotypes and an increased NSCL/P risk.

Conclusions: In contrast to other Asian populations, our study indicates that the IRF6 rs642961 polymorphism cannot be a risk factor for NSCL/P in an Iranian population.

Clinical Relevance: Genetic factors have an important role in NSCL/P, among which interferon regulatory factor 6 (IRF6) has been reported as a risk factor for NSCL/P in several populations; however, our data indicated no significant association between IRF6 polymorphism and NSCL/P in an Iranian population.
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http://dx.doi.org/10.1007/s00784-014-1305-3DOI Listing
May 2015

Genotype-phenotype correlation of survival motor neuron and neuronal apoptosis inhibitory protein genes in spinal muscular atrophy patients from Iran.

Adv Biomed Res 2014 27;3:74. Epub 2014 Jan 27.

Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran ; Pediatric Inherited Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Proximal spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by symmetrical proximal muscle weakness and atrophy. According to the severity of the disease and the age of onset, SMA can be divided into three groups. The survival motor neuron (SMN) gene that is located on 5q13 is identified as the disease determining gene. Another gene in this region is neuronal apoptosis inhibitory protein (NAIP), and its functional role in the pathogenesis of SMA has not been fully elucidated. Here, we investigated the correlation between deletions in SMN and NAIP genes with clinical features of SMA patients.

Materials And Methods: In the current study, 71 unrelated Iranian patients were investigated for the detection of deletions in SMN1 and NAIP genes. Polymerase chain reaction (PCR) was used to detect the deletions of exon 4 and 5 of the NAIP gene. Deletions in exon 7 and 8 of SMN1 gene were detected by RFLP-PCR with DraI and DdeI, respectively.

Results: Our results showed that 51 patients have homozygous deletions in SMN1 and/or NAIP genes. Among these 51 patients, deletion in NAIP gene were found in 35 patients (65.7% of type I, 22.5% type II and 11.42% type III).

Conclusion: Defect in SMN1 gene plays a major role in manifesting of the disease and NAIP (4 and 5) gene acts as a modifying factor in severity of symptoms. Correlation between NAIP gene defect and severity of the disease is confirmed. However, the exact role of NAIP gene in SMA has yet to be fully clarified.
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http://dx.doi.org/10.4103/2277-9175.125872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950840PMC
March 2014

Evaluation of multiplex ligation-dependent probe amplification analysis versus multiplex polymerase chain reaction assays in the detection of dystrophin gene rearrangements in an Iranian population subset.

Adv Biomed Res 2014 27;3:72. Epub 2014 Jan 27.

Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran ; Pediatric Inherited Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran ; Pediatric Neurology, Pediatric Neurology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: The Duchenne muscular dystrophy (DMD) gene is located in the short arm of the X chromosome (Xp21). It spans 2.4 Mb of the human genomic DNA and is composed of 79 exons. Mutations in the Dystrophin gene result in DMD and Becker muscular dystrophy. In this study, the efficiency of multiplex ligation-dependent probe amplification (MLPA) over multiplex polymerase chain reaction (PCR) assays in an Iranian population was investigated.

Materials And Methods: Multiplex PCR assays and MLPA analysis were carried out in 74 patients affected with DMD.

Results: Multiplex PCR detected deletions in 51% of the patients with DMD. MLPA analysis could determine all the deletions detected by the multiplex PCR. Additionally, MLPA was able to identify one more deletion and duplication in patients without detectable mutations by multiplex PCR. Moreover, MLPA precisely determined the exact size of the deletions.

Conclusion: Although MLPA analysis is more sensitive for detection of deletions and duplications in the dystrophin gene, multiplex PCR might be used for the initial analysis of the boys affected with DMD in the Iranian population as it was able to detect 95% of the rearrangements in patients with DMD.
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http://dx.doi.org/10.4103/2277-9175.125862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950794PMC
March 2014

Detection of intragenic SMN1 mutations in spinal muscular atrophy patients with a single copy of SMN1.

J Child Neurol 2015 Apr 20;30(5):558-62. Epub 2014 Feb 20.

Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

Proximal spinal muscular atrophy is an autosomal recessive disorder characterized by symmetrical muscle weakness due to degeneration of alpha motor neurons in the spinal cord. Homozygous deletions in the SMN1 have been reported in more than 90% of spinal muscular atrophy cases. Compound heterozygous patients account for approximately 4% of spinal muscular atrophy cases. In this study, we performed a quantitative test in 20 of 87 spinal muscular atrophy patients who did not have homozygous deletion of SMN1. Mutation screening of SMN1 gene was performed in 4 patients who have only 1 copy of SMN1 to identify intragenic mutations. In addition to a previously described missense mutation in exon 4 (p.A188S/ c.562G>T), we identified 2 novel mutations including a single nucleotide insertion in exon 7 (c.861_862insT/p.R288X) and a deletion of nucleotide G in exon 3 (c.286delG/p.D96Tfs*53). Our results suggested that about 4% of spinal muscular atrophy patients have subtle mutations and might be considered in laboratory examination.
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http://dx.doi.org/10.1177/0883073814521297DOI Listing
April 2015

Use of in silico tools for classification of novel missense mutations identified in dystrophin gene in developing countries.

Gene 2014 Feb 22;535(2):250-4. Epub 2013 Nov 22.

Pediatric Inherited Disease Research Center (PIDRC), Isfahan University of Medical Sciences, Isfahan, Iran; Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

DMD gene which is composed of 79 exons is the largest known gene located on X chromosome (Xp21). Point mutations in the dystrophin gene are responsible for 30-35% of cases with DMD/BMD. Mutation analysis of all the exons of the DMD gene is costly in developing countries, therefore, a few of the exons are selected to be analyzed routinely in clinical laboratories. In this study, direct sequencing was used for detection of point mutations in 10 exons of dystrophin gene in patients affected with DMD without detectable large rearrangements. Freely available programs were used to predict the damaging effects of the mutations. Point mutations were successfully detected in three patients. Three novel mutations, two missense mutations located on nonconservative domains and a single nucleotide deletion, were detected. Missense mutations were predicted to change splicing efficiency. Detection of point mutations by DNA analysis followed by prediction of the pathogenecity by using bioinformatic tool might be an asset to provide proper diagnosis or genetic counseling to patients and their family.
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http://dx.doi.org/10.1016/j.gene.2013.11.022DOI Listing
February 2014

Mutation analysis of CACNA1A gene in Iranian migrainous and review literatures.

J Res Med Sci 2013 Mar;18(Suppl 1):S6-S10

Isfahan Neurosciences Research Center, Isfahan University of Medical Science, Isfahan, Iran ; Department of Medical Sciences, Islamic Azad University, Najaf Abad Branch, Isfahan, Iran.

Background: There are contrary results about the role of CACNA1A gene in the causation of common migraine in different populations. However, migraine may be genetically heterogeneous and more studies in different families and populations are required for a definite conclusion. The aim of this study was to surveyed leukocyte genomic DNA mutation of CACNA1A in Iranian migraine patients with [MA] and without aura [MO] who has family history of migraine and we performed a narrative review of all studies that evaluated CACNA1A gene, non-hemiplegic migraine [MA and MO] and FHM [familial hemiplegic migraine].

Materials And Methods: The 30 patients with family history of migraine were selected for mutations analysis for CACNA1A gene by PCR method. For review, we searched MEDLINE-PUBMED, ISI, Scopus and Cochrane databases up to December 2012.

Results: Mutation analysis of the 4 exons of the CACNA1A gene in these patients revealed no mutations in this gene. Direct sequencing revealed a polymorphism previously reported G to A transition in the exon 16 [nt2369, G→A] in 9 patients. In review, the correlation of FHM loci [CACNA1A gene] with MA and MO has been showed in different population and only small population from Caucasians presented this correlation.

Conclusion: CACNA1A is most likely not a major susceptibility gene for common migraine in Iranian maigrainous. It's essential to study more on larger series and covering all 47 exons of the CACNA1A gene to confirm this hypothesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743323PMC
March 2013

An insight into genetics of non-syndromic cleft palate.

Adv Biomed Res 2013 6;2. Epub 2013 Mar 6.

Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran ; Pediatric Inherited Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Our proband is a 29-year-old man, who is affected with soft cleft palate and hypernasality. A study of about six generations of this family pedigree shows that cleft palate has repeatedly occurred in males, with probably a X-linked recessive pattern of inheritance. Interestingly, the sister of the proband is affected with hypernasality and she has an affected son. This is the first report of X-linked inheritance pattern of cleft palate in Iran.
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http://dx.doi.org/10.4103/2277-9175.107969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732890PMC
August 2013

Cutis laxa type II with mutation in the pyrroline-5-carboxylate reductase 1 gene.

Pediatr Dermatol 2013 Nov-Dec;30(6):e265-7. Epub 2013 Feb 14.

Molecular Genetic Laboratory, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; Pediatric Inherited Disease Research Center, Isfahan, Iran.

A 14-year-old Iranian boy with congenital cutis laxa and several other typical autosomal recessive type II features was examined. Mutation analysis of the pyrroline-5-carboxylate reductase 1 gene revealed a single-base deletion (c.345delC) in exon 4 leading to frame shift and premature termination of translation.
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http://dx.doi.org/10.1111/pde.12065DOI Listing
August 2014

Investigation of TBX1 gene deletion in Iranian children with 22q11.2 deletion syndrome: correlation with conotruncal heart defects.

Heart Asia 2013 12;5(1):200-2. Epub 2013 Sep 12.

Department of Plastic and Reconstructive Surgery , Alzahra University Hospital, Isfahan University of Medical Sciences , Isfahan , Iran.

Background: DiGeorge syndrome (DGS) is the result of a microdeletion in chromosome 22q11.2 in over 90% of cases. DGS is the second most frequent syndrome after Down syndrome and has an incidence of 1/4000 births. Unequal crossover between low-copy repeats, on the proximal part of the long arm of chromosome 22, usually results in a 3 Mb deletion in one of the chromosome 22 and a reciprocal and similarly sized duplication on the other one. Several studies have indicated that TBX1 (T-box 1) haploinsufficiency is responsible for many of the phenotypic traits of 22q11.2 deletion syndrome. Conotruncal heart defects (CTDs) are present in 75-85% of patients with 22q11.2 deletion syndrome in Western countries.

Methods: Among 78 patients fulfilling the criteria for DGS diagnosed by the fluorescence in situ hybridisation test, 24 had 22q11.2 deletion. Screening for TBX1 gene deletion was performed by multiplex ligation-dependent probe amplification (MLPA).

Results: Our results revealed that of 24 patients with TBX1 gene deletion, 12 had CTDs while 12 did not show any heart defects.

Conclusions: Our findings indicate that other genes or gene interactions may play a role in penetrance or the severity of heart disease among patients with DGS.
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http://dx.doi.org/10.1136/heartasia-2013-010327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832817PMC
June 2016

A case report of 22q11 deletion syndrome confirmed by array-CGH method.

J Res Med Sci 2012 Mar;17(3):310-2

Molecular Genetics Laboratory, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.

Velo-cardio-facial syndrome (VCFS) is caused by a submicroscopic deletion on the long arm of chromosome 22 and affects approximately 1 in 4000 persons, making it the second most prevalent genetic syndrome after Down syndrome and the most common genetic syndrome associated with cleft palate. Most of the 22q11.2 deletion cases are new occurrences or sporadic; however, in about 10 % of families, the deletion is inherited and other family members are affected or at risk for passing this deletion to their children. This report describes a 1.5 years-old male child with clinical signs of velo-cardio-facial syndrome (VCFS) presented with heart defect, soft cleft palate, developmental delay, acrocephaly, seizure, MRI abnormalities and descriptive facial feature, such as hypertelorism. Array-CGH test was done to confirm the diagnosis; the result revealed a 2.6 Mbp deletion in 22q11.2 chromosome that containing TBX1 and COMT genes. Our data suggest that haploinsufficiency of TBX1 gene is probably a major contributor to some of the syndrome characteristic signs, such as heart defect. Because of developmental delay and dysmorphic facial feature were observed in the index's mother and relatives, inherited autosomal dominant form of VCF is probable, and MLPA (multiplex ligation-dependent probe amplification) test should be performed for parents to estimate the recurrent risk in next pregnancy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527053PMC
March 2012

A novel mutation in the aprataxin (APTX) gene in an Iranian individual suffering early-onset ataxia with oculomotor apraxia type 1(AOA1) disease.

Iran Biomed J 2012 ;16(4):223-5

Dept. of Genetics, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

Background: Ataxia with oculomotor apraxia type 1 (AOA1) shows early onset with autosomal recessive inheritance and is caused by a mutation in the aprataxin (APTX) gene encoding for the APTX protein.

Methods: In this study, a 7-year-old girl born of a first-cousin consanguineous marriage was described with early-onset progressive ataxia and AOA, with increased cholesterol concentration and decreased albumin concentration in serum. PCR and direct DNA sequencing was performed after DNA extraction.

Results: Sequencing analysis revealed a novel homozygous deletion in c.643 and A>T single nucleotide polymorphism in c.641 in exon 6 of the APTX gene [ENST00000379825].

Conclusion: It seems that this region of exon 6 is probably a hot spot; however, no deletions have been reported in exon 6 yet.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3600965PMC
http://dx.doi.org/10.6091/ibj.1077.2012DOI Listing
June 2013

Association between mismatch repair gene MSH3 codons 1036 and 222 polymorphisms and sporadic prostate cancer in the Iranian population.

Asian Pac J Cancer Prev 2012 ;13(12):6055-7

Young Researcher Club. I.A.U. Falavarjan University, Iran E-mail :

The mismatch repair system (MMR) is a post-replicative DNA repair mechanism whose defects can lead to cancer. The MSH3 protein is an essential component of the system. We postulated that MSH3 gene polymorphisms might therefore be associated with prostate cancer (PC). We studied MSH3 codon 222 and MSH3 codon 1036 polymorphisms in a group of Iranian sporadic PC patients. A total of 60 controls and 18 patients were assessed using the polymerase chain reaction and single strand conformational polymorphism. For comparing the genotype frequencies of patients and controls the chi-square test was applied. The obtained result indicated that there was significantly association between G/A genotype of MSH3 codon 222 and G/G genotype of MSH3 codon 1036 with an increased PC risk (P=0.012 and P=0.02 respectively). Our results demonstrated that MSH3 codon 222 and MSH3 codon 1036 polymorphisms may be risk factors for sporadic prostate cancer in the Iranian population.
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http://dx.doi.org/10.7314/apjcp.2012.13.12.6055DOI Listing
April 2016