Publications by authors named "Aliasgar Mohammadi"

4 Publications

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Molecular Genetic Study in a Cohort of Iranian Families Suspected to Maturity-Onset Diabetes of the Young, Reveals a Recurrent Mutation and a High-Risk Variant in the Gene.

Adv Biomed Res 2020 27;9:25. Epub 2020 Jun 27.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Diabetes mellitus (DM) is a group of metabolic disorders in the body, accompanied with increasing blood sugar levels. Diabetes is classified into three groups: Type 1 DM (T1DM), Type 2 DM (T2DM), and monogenic diabetes. Maturity-onset diabetes of the young (MODY) is a monogenic diabetes that is frequently mistaken for T1D or T2D. The aim of this study was to diagnose MODY and its subtype frequency in a diabetic population in Iran.

Materials And Methods: In this study among ten diabetic families that were highly suspected to MODY by nongenetic biomarkers and without any pathogenic mutation in and genes, two patients from two unrelated families were examined via whole-exome sequencing (WES) in order to detect the causative gene of diabetes. Co-segregation analysis of the identified variant was performed using Sanger sequencing.

Results: In this study, no pathogenic variant was found in and genes (MODY2 and MODY3), while these two types of MODY were introduced as the most frequent in other studies. By using WES, a pathogenic variant (p.I488T) was found in one of the patients in gene causing MODY8 that its frequency is very rare in other studied populations. A high-risk variant associated with diabetes was found in another patient.

Conclusion: WES was applied in this study to reveal the cause of MODY in 1 family. This pathogenic mutation was previously reported as a disease causing mutation.
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http://dx.doi.org/10.4103/abr.abr_18_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532821PMC
June 2020

A pathogenic variant in the transforming growth factor beta I () in four Iranian extended families segregating granular corneal dystrophy type II: A literature review.

Iran J Basic Med Sci 2020 Aug;23(8):1020-1027

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Objectives: Granular and lattice corneal dystrophies (GCDs & LCDs) are autosomal dominant inherited disorders of the cornea. Due to genetic heterogeneity and large genes, unraveling the mutation is challenging.

Materials And Methods: Patients underwent comprehensive clinical examination, and targeted next-generation sequencing (NGS) was used for mutation detection. Co-segregation and analysis was accomplished.

Results: Patients suffered from GCD. NGS disclosed a known pathogenic variant, c.371G>A (p.R124H), in exon 4 of . The variant co-segregated with the phenotype in the family. Homozygous patients manifested with more severe phenotypes. Variable expressivity was observed among heterozygous patients.

Conclusion: The results, in accordance with previous studies, indicate that the c.371G>A in TGFBI is associated with GCD. Some phenotypic variations are related to factors such as modifier genes, reduced penetrance and environmental effects.
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http://dx.doi.org/10.22038/ijbms.2020.36763.8757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478261PMC
August 2020

Genetic Study of Hepatocyte Nuclear Factor 1 Alpha Variants in Development of Early-Onset Diabetes Type 2 and Maturity-Onset Diabetes of the Young 3 in Iran.

Adv Biomed Res 2019 23;8:55. Epub 2019 Sep 23.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous group of diabetes characterized by noninsulin-dependent, autosomal-dominant disorder with strong familial history, early age of onset, and pancreatic beta-cell dysfunction. Mutations in at least 14 different genes are responsible for various MODY subtypes. Heterozygous mutations in the hepatocyte nuclear factor 1 alpha () gene are responsible for the MODY3 subtype, which is a common subtype of MODY in different studied populations. To date, more than 450 different variants of this gene have been reported as disease causing for MODY3. This study was carried out to evaluate mutations in Iranian diabetic families fulfilling MODY criteria.

Materials And Methods: Polymerase chain reaction and Sanger sequencing were performed. All the ten exons of the gene were sequenced in ten families, followed by cosegregation analysis and evaluation. Computational protein modeling was accomplished for the identified mutation.

Results: MODY3 was confirmed in two large families by detecting a mutation (p.G253E) in coding regions of . Compound heterozygous state for two common variants in (p.I27 L and p.S487N) was detected in affected members of 5 families, and in one family, a rare benign variant in the coding sequence for Kozak sequence was detected. Two new nonpathogenic variants were found in noncoding regions of .

Conclusion: It seems that mutations are a common cause of MODY in Iranian diabetic patients. Identified common variants in heterozygous state can cause diabetes Type II in earlier ages. The role of rare variant rs3455720 is unknown, and more investigation is needed to uncover the function of this variant.
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http://dx.doi.org/10.4103/abr.abr_54_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777141PMC
September 2019

A novel pathogenic variant in the FZD6 gene causes recessive nail dysplasia in a large Iranian kindred.

J Dermatol Sci 2017 Oct 13;88(1):134-138. Epub 2017 May 13.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Background: Nail disorder nonsyndromic congenital (NDNC) is a very rare clinically and genetically heterogeneous disease inherited both in recessive or dominant modes. FZD6 is a component of Wnt-FZD signaling pathway in which recessive loss-of-function variants in the corresponding genes could lead to nail anomalies.

Objective: A large multiplex family with NDNC was referred for genetic counselling. Thorough genetic evaluation was performed.

Methods: PCR-Sanger sequencing was carried out for the coding exons and exon-intron boundaries of the FZD6 gene. Co-segregation analysis, in silico evaluation and computational protein modeling was accomplished.

Results: A homozygous 1bp deletion variant, c.1859delC (p.Ser620Cysfs*75), leading to a truncating protein was found in the patient. Parents were heterozygous for the variant. The variant was found to be co-segreagting with the phenotype in the family. Computational analysis and protein modeling revealed its pathogenic consequence by disturbing the cytoplasmic domain structure and signaling through loss of phosphorylation residues. The variant met the criteria of being pathogenic according to the ACMG guideline.

Conclusions: This is the first report of the genetic diagnosis of NDNC in Iran. We also report a novel pathogenic variant. The study of the FZD6 gene is recommended as the first step in the diagnostic routing of the autosomal recessive NDNC patients with enlarged nails.
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http://dx.doi.org/10.1016/j.jdermsci.2017.04.017DOI Listing
October 2017