A transversion mutation in non-coding exon 3 of the TMC1 gene in two ethnically related Iranian deaf families from different geographical regions; evidence for founder effect

Davoudi-Dehaghani, Elham; Zeinali, Sirous; Mahdieh, Nejat; Shirkavand, Atefeh; Bagherian, Hamideh; Tabatabaiefar, Mohammad Amin

doi:10.1016/j.ijporl.2013.02.021

Cited by 21 publications

(7 citation statements)

References 32 publications

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“…In the study on 144 GJB2 -negative subjects, using linkage analysis and direct sequencing, 4 out of 144 families (2.7%) were linked to DFNB7-11(19). Moreover, Dehaghani et al (32), using homozygosity mapping on 45 ARNSHL families, detected 1family (2.2%) to be linked to DFNB7/11. Therefore, the locus could be one common causes of ARNSHL in the west of Iran.…”

Section: Discussionmentioning

confidence: 99%

Screening of 10 DFNB Loci Causing Autosomal Recessive Non-Syndromic Hearing Loss in Two Iranian Populations Negative for GJB2 Mutations

Koohiyan

Reiisi

Azadegan‐Dehkordi

et al. 2020

ijph

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Background: Autosomal recessive non-syndromic hearing loss (ARNSHL), one of the global public health concerns, is marked by a high degree of genetic heterogeneity. The role of GJB2, as the most common cause of ARNSHL, is only <20% in the Iranian population. Here, we aimed to determine the relative contribution of several apparently most common loci in a cohort of ARNSHL Iranian families that were negative for the GJB2 mutations. Methods: Totally, 80 Iranian ARNSHL families with 3 or more affected individuals from Isfahan and Hamedan provinces, Iran were enrolled in 2017. After excluding mutations in the GJB2 gene via Sanger sequencing, 60 negative samples (30 families from each province) were analyzed using homozygosity mapping for 10 ARNSHL loci. Results: Fourteen families were found to be linked to five different known loci, including DFNB4 (5 families), DFNB2 (3 families), DFNB7/11 (1 family), DFNB9 (2 families) and DFNB3 (3 families). Conclusion: Despite the high heterogeneity of ARNSHL, the genetic causes were determined in 23.5% of the studied families using homozygosity mapping. This data gives an overview of the ARNSHL etiology in the center and west of Iran, used to establish a diagnostic gene panel including most common loci for hearing loss diagnostics.

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Section: Discussionmentioning

confidence: 99%

Screening of 10 DFNB Loci Causing Autosomal Recessive Non-Syndromic Hearing Loss in Two Iranian Populations Negative for GJB2 Mutations

Koohiyan

Reiisi

Azadegan‐Dehkordi

et al. 2020

ijph

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“…We have previously reported pathogenic variants in some genetic disorders in our population. Specific pathogenic variants have been observed with high frequencies in some populations in many disorders, e.g., common pathogenic variants in CYP21A2 and GJB2 genes in different ethnicities living in Iran (Davoudi-Dehaghani et al, 2013;Mahdieh et al [2016]; Rabbani et al [2011]).…”

Section: Discussionmentioning

confidence: 99%

TPP1 Variants in Iranian patients: A Novel Pathogenic Homozygous Variant Causing Neuronal Ceroid Lipofuscinosis 2

Vafaei,

Mohebbi,

Rezaei

et al. 2023

Mol Syndromol

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Introduction: TPP1 variants have been identified as a causative agent of neuronal ceroid lipofuscinosis 2 disease, that ataxia is one of its clinical features. Therefore, here, molecular study of TPP1 variants is presented in an Iranian cohort and a novel pathogenic variant is described. Methods: This investigation was conducted as a cross-sectional study in a tertiary referral hospital, Children’s Medical Center, Pediatrics Center of Excellence. Clinical presentations and pedigrees were documented. Patients with cerebellar ataxia were enrolled in this study. Next-generation sequencing was applied to confirm the diagnosis. Segregation and bioinformatics analyses were also done for the variants using Sanger sequencing. Results: Forty-five patients were included in our study. The mean age of onset was 104 (+55.60) months (minimum = 31 months, maximum = 216 months). The majority of cases (73.3%) were born to consanguineous parents and only 1 patient (2.2%) had an affected sibling. Of the 45 patients, only 1 patient with a novel pathogenic variant (c.1425_1425+1delinsAT, p.A476Cfs*15) in the TPP1 gene was identified. Discussion: The main strength of current study is the relatively large sample size. Besides, a novel pathogenic variant could be important toward the diagnosis and management of this condition. With significant advances in various therapies, early diagnosis could improve the treatments using personalized-based medicine.

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“…Homozygous or compound heterozygous variants in the gap junction beta-2 ( GJB2 ) gene and large deletions in the gap junction beta-6 ( GJB6 ) gene are the common causes of HL in Iran and many other countries [ 5 – 7 ]. Furthermore, according to previous studies in Iran, mutations in the solute carrier family 26 member 4 ( SLC26A4) gene [ 8 ] is another common cause of NSHL followed by mutations in Myosin XVA ( MYO15A ) [ 9 ] Myosin VIIA ( MYO7A ) [ 7 ], Cadherin related 23 ( CDH23 ) [ 10 ], Protocadherin related 15 ( PCDH15 ) [ 10 ], alpha-Tectorin ( TECTA ) [ 11 ], Pejvakin ( PJVK ) [ 12 ], transmembrane channel-like protein 1 ( TMC1 ) [ 13 ], Leucine-rich transmembrane and O-methyltransferase domain-containing ( LRTOMT ) [ 14 ], immunoglobulin-like domain-containing receptor 1 ( ILDR1 ) [ 15 ], MARVEL domain containing 2 ( MARVELD2 ) [ 7 ], Otoferlin ( OTOF ) [ 7 ], Radixin ( RDX ) [ 7 ], Lipoxygenase homology PLAT domains 1 ( LOXHD1 ) [ 16 ], and Collagen type XI alpha 2 chain ( COL11A2 ) genes [ 17 ]. According to Bazazzadegan et al study in Iran, the prevalence of GJB2 mutations varies based on geographical location and ethnicity; for example, in Azerbaijan provinces (northwest of Iran where our study was done), GJB2 mutations account for 22% of HL cases whereas, in Sistan and Baluchestan province (southeast of Iran with Baluch ethnicity), this amount is only 8% [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

A novel missense variant in ESRRB gene causing autosomal recessive non-syndromic hearing loss: in silico analysis of a case

et al. 2022

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Background Hereditary hearing loss (HHL) is a common heterogeneous disorder affecting all ages, ethnicities, and genders. The most common form of HHL is autosomal recessive non-syndromic hearing loss (ARNSHL), in which there is no genotype–phenotype correlation in the majority of cases. This study aimed to identify the genetic causes of hearing loss (HL) in a family with Iranian Azeri Turkish ethnicity negative for gap junction beta-2 (GJB2), gap junction beta-6 (GJB6), and mitochondrially encoded 12S rRNA (MT-RNR1) deleterious mutations. Methods Targeted genome sequencing method was applied to detect genetic causes of HL in the family. Sanger sequencing was employed to verify the segregation of the variant. Finally, we used bioinformatics tools and American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines to determine whether the detected variant might affect the corresponding protein or not. Results A novel homozygous missense mutation, c.499G>A (p.G167R), was identified in exon 5 of the ESRRB (estrogen-related receptor beta) gene. Healthy and affected family members confirmed the co-segregation of the variant with ARNSHL. Eventually, the variant's pathogenicity was confirmed by the in silico analysis and the ACMG/AMP guidelines. Conclusion The study suggests that the detected variant, c.499G>A, plays a crucial role in the development of ARNSHL, emphasizing the clinical significance of the ESRRB gene in ARNSHL patients. Additionally, it would be helpful for genetic counseling and clinical management of ARNSHL patients and providing preventive opportunities.

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A transversion mutation in non-coding exon 3 of the TMC1 gene in two ethnically related Iranian deaf families from different geographical regions; evidence for founder effect

Cited by 21 publications

References 32 publications

Screening of 10 DFNB Loci Causing Autosomal Recessive Non-Syndromic Hearing Loss in Two Iranian Populations Negative for GJB2 Mutations

Screening of 10 DFNB Loci Causing Autosomal Recessive Non-Syndromic Hearing Loss in Two Iranian Populations Negative for GJB2 Mutations

<i>TPP1</i> Variants in Iranian patients: A Novel Pathogenic Homozygous Variant Causing Neuronal Ceroid Lipofuscinosis 2

A novel missense variant in ESRRB gene causing autosomal recessive non-syndromic hearing loss: in silico analysis of a case

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