Publications by authors named "Najmeh Fattahi"

4 Publications

  • Page 1 of 1

A pathogenic variant in is associated with Pendred syndrome in a consanguineous Iranian family.

Int J Audiol 2019 10 12;58(10):628-634. Epub 2019 Jun 12.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences , Shahrekord , Iran.

Hearing loss (HL) is a common sensory deficit with high phenotypic and genotypic heterogeneity. A large Iranian family with HL was genetically assessed in this study. A proband from a consanguineous multiplex HL family from Iran was examined via Targeted Next-Generation Sequencing (TNGS). Sanger sequencing allowed the segregation analysis of the variant of interest and the investigation of its presence in a cohort of 50 ethnicity-matched healthy control individuals. The gene was previously associated with HL. Therefore, to determine whether the variant was specifically associated with Pendred Syndrome (PDS) or DFNB4, biochemical analyses, PTA, thyroid scans by Tc99m, perchlorate discharge test and high-resolution CT scan of the temporal bone were carried out on the affected family members. Ten members of a large multiplex Iranian family with HL were recruited in this study. In addition, 50 unrelated healthy controls of the same ethnic group were randomly selected to genotype the variant. A homozygous missense variant (NM_000441.1: c.1211C > T/p.Thr404Ile) in exon 10 was found segregating in the family. Based on the ACMG's guidelines, the variant was classified as pathogenic. This study expands the spectrum of pathogenic variants in hearing loss.
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http://dx.doi.org/10.1080/14992027.2019.1619945DOI Listing
October 2019

Next-generation sequencing reveals a novel pathological mutation in the TMC1 gene causing autosomal recessive non-syndromic hearing loss in an Iranian kindred.

Int J Pediatr Otorhinolaryngol 2019 Sep 21;124:99-105. Epub 2019 May 21.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

Objectives: Hearing loss (HL) is the most common sensory-neural disorder with excessive clinical and genetic heterogeneity, which negatively affects life quality. Autosomal recessive non-syndromic hearing loss (ARNSHL) is the most common form of the disease with no specific genotype-phenotype correlation in most of the cases. Whole exome sequencing (WES) is a powerful tool to overcome the problem of finding mutations in heterogeneous disorders.

Methods: A comprehensive clinical and pedigree examination was performed on a multiplex family from Khuzestan province suffering from hereditary HL. Direct sequencing of GJB2 and genetic linkage analysis of DFNB1A/B was accomplished. WES was utilized to find possible genetic etiology of the disease. Co-segregation analysis of the candidate variant was done. High resolution melting analysis was applied to detect variant status in 50 healthy matched controls.

Results: Clinical investigations suggested ARNSHL in the pedigree. The family was negative for DFNB1A/B. WES revealed a novel nonsense mutation, c.256G > T (p.Glu86*), in TMC1 segregating with the phenotype in the pedigree. The variant was absent in the controls.

Conclusion: Here, we report successful application of WES to identify the molecular pathogenesis of ARNSHL in a large family. The novel nonsense TMC1 variant meets the criteria of being pathogenic according to the ACMG-AMP variant interpretation guideline.
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http://dx.doi.org/10.1016/j.ijporl.2019.05.023DOI Listing
September 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.
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http://dx.doi.org/10.1002/jcb.27607DOI Listing
March 2019

A novel pathogenic variant in an Iranian Ataxia telangiectasia family revealed by next-generation sequencing followed by in silico analysis.

J Neurol Sci 2017 Aug 12;379:212-216. Epub 2017 Jun 12.

Ahvaz Noor Genetics Laboratory, Ahvaz, Iran; Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address:

Ataxia telangiectasia (A-T) is a neurodegenerative autosomal recessive disorder with the main characteristics of progressive cerebellar degeneration, sensitivity to ionizing radiation, immunodeficiency, telangiectasia, premature aging, recurrent sinopulmonary infections, and increased risk of malignancy, especially of lymphoid origin. Ataxia Telangiectasia Mutated gene, ATM, as a causative gene for the A-T disorder, encodes the ATM protein, which plays an important role in the activation of cell-cycle checkpoints and initiation of DNA repair in response to DNA damage. Targeted next-generation sequencing (NGS) was performed on an Iranian 5-year-old boy presented with truncal and limb ataxia, telangiectasia of the eye, Hodgkin lymphoma, hyper pigmentation, total alopecia, hepatomegaly, and dysarthria. Sanger sequencing was used to confirm the candidate pathogenic variants. Computational docking was done using the HEX software to examine how this change affects the interactions of ATM with the upstream and downstream proteins. Three different variants were identified comprising two homozygous SNPs and one novel homozygous frameshift variant (c.80468047delTA, p.Thr2682ThrfsX5), which creates a stop codon in exon 57 leaving the protein truncated at its C-terminal portion. Therefore, the activation and phosphorylation of target proteins are lost. Moreover, the HEX software confirmed that the mutated protein lost its interaction with upstream and downstream proteins. The variant was classified as pathogenic based on the American College of Medical Genetics and Genomics guideline. This study expands the spectrum of ATM pathogenic variants in Iran and demonstrates the utility of targeted NGS in genetic diagnostics.
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http://dx.doi.org/10.1016/j.jns.2017.06.012DOI Listing
August 2017