Publications by authors named "Azam Ahmadi Shadmehri"

5 Publications

  • Page 1 of 1

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22038/ijbms.2020.36763.8757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478261PMC
August 2020

Mutations in PLOD3, encoding lysyl hydroxylase 3, cause a complex connective tissue disorder including recessive dystrophic epidermolysis bullosa-like blistering phenotype with abnormal anchoring fibrils and type VII collagen deficiency.

Matrix Biol 2019 08 18;81:91-106. Epub 2018 Nov 18.

Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA; Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address:

Epidermolysis bullosa (EB), the paradigm of heritable skin fragility disorders, is associated with mutations in as many as 20 distinct genes. One of the clinical variants, recessive dystrophic EB (RDEB), demonstrates sub-lamina densa blistering accompanied by alterations in anchoring fibrils due to mutations in COL7A1. In this study, we characterized a patient with widespread connective tissue abnormalities, including skin blistering similar to that in RDEB. Whole exome sequencing, combined with genome-wide homozygosity mapping, identified a homozygous missense mutation in PLOD3 encoding lysyl hydroxylase 3 (LH3). No mutations in COL7A1, the gene previously associated with RDEB, were detected. The level of LH3 was dramatically reduced in the skin and fibroblast cultures from the patient. The blistering in the skin occurred below the lamina densa and was associated with variable density and morphology of anchoring fibrils. The level of type VII collagen expression in the skin was markedly reduced. Analysis of hydroxylysine and its glycosylated derivatives (galactosyl-hydroxylysine and glucosyl-galactosyl-hydroxylysine) revealed marked reduction in glycosylated hydroxylysine. Collectively, these findings indicate that PLOD3 mutations can result in a dystrophic EB-like phenotype in the spectrum of connective tissue disorders and add it to the list of candidate genes associated with skin fragility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.matbio.2018.11.006DOI Listing
August 2019

Molecular genetic study of glutaric aciduria, type I: Identification of a novel mutation.

J Cell Biochem 2019 03 11;120(3):3367-3372. Epub 2018 Sep 11.

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

Glutaric acidemia type I (GA-1) is an inborn error of metabolism due to deficiency of glutaryl-CoA dehydrogenase (GCDH), which catalyzes the conversion of glutaryl-CoA to crotonyl-CoA. GA-1 occurs in about 1 in 100 000 infants worldwide. The GCDH gene is on human chromosome 19p13.2, spans about 7 kb and comprises 11 exons and 10 introns. Tandem mass spectrometry (MS/MS) was used for clinical diagnosis in a proband from Iran with GA-1. Sanger sequencing was performed using primers specific for coding exons and exon-intron flanking regions of the GCDH gene in the proband. Cosegregation analysis and in silico assessment were performed to confirm the pathogenicity of the candidate variant. A novel homozygous missense variant c.1147C > A (p.Arg383Ser) in exon 11 of GCDH was identified. Examination of variant through in silico software tools determines its deleterious effect on protein in terms of function and stability. The variant cosegregates with the disease in family. In this study, the clinical and molecular aspects of GA-1 were investigated, which showed one novel mutation in the GCDH gene in an Iranian patient. The variant is categorized as pathogenic according to the the guideline of the American College of Medical Genetics and Genomics (ACMG) for variant interpretation. This mutation c.1147C > A (p.Arg383Ser) may also be prevalent among Iranian populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.27607DOI Listing
March 2019

Identification of a combined missense/splice-site mutation in FAH causing tyrosinemia type 1.

J Pediatr Endocrinol Metab 2014 Jul;27(7-8):795-8

Tyrosinemia type I (HT1) is a genetic metabolic disorder characterized by progressive liver disease, kidney disease, and rickets. The disease is caused by mutations in the FAH gene that results in deficiency of fumarylacetoacetase, an enzyme that is involved in the tyrosine degradation pathway. We investigated the clinical characteristics and molecular cause of HT1 in an affected family from Iran. Molecular analysis identified a homozygous combined missense (c.G1009G>A, p.Gly337Ser) and aberrant splicing mutation removing the first 50 nucleotides of exon 12. This mutation was only described in HT1 patients from Scandinavian countries and this is the first report from another population. Although failure to thrive is one of the typical features in HT1, our proband, similar to the reported Scandinavian patients, had normal growth and development. The results of this study have applications in patient screening and genetic counselling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/jpem-2013-0489DOI Listing
July 2014

Identification of two HEXA mutations causing infantile-onset Tay-Sachs disease in the Persian population.

J Hum Genet 2011 Sep 28;56(9):682-4. Epub 2011 Jul 28.

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

The β-hexosaminidase A (HEXA) mutations in the first reported cases of infantile Tay-Sachs disease in the Persian population were identified in two unrelated consanguineous families. The clinical diagnoses of the affected infants were confirmed by their markedly deficient levels of HEXA activity in plasma or peripheral leukocytes. The specific causative mutation in each family was determined by sequencing the HEXA alleles in both sets of related parents. Two mutations were identified: c.1A>G (p.MIV), which obliterated the initiating methionine in codon 1, and c.1177C>T (p.R393X), which predicted a termination codon or nonsense mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/jhg.2011.78DOI Listing
September 2011