Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next‐generation sequencing

Bitarafan, Fatemeh; Seyedena, Seyed Yousef; Mahmoudi, Mahdi; Garshasbi, Masoud

doi:10.1002/jcla.23544

Cited by 10 publications

(4 citation statements)

References 42 publications

(98 reference statements)

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“…In summary, GIPC3 mutations have been shown to underlie NSHL associated with DFNB15 , DFNB72 and DFNB95 . In NSHL, biallelic, nonsense, and shift mutations were also observed in the GIPC3 gene ( Chen et al, 1997 ; Ain et al, 2007 ; Charizopoulou et al, 2011 ; Rehman et al, 2011 ; Diaz-Horta et al, 2012 ; Sirmaci et al, 2012 ; Ramzan et al, 2013 ; Petrova et al, 2021 ), and more GIPC3 mutation loci are gradually being reported as research progresses ( Siddiqi et al, 2014 ; Ammar-Khodja et al, 2015 ; Asgharzade et al, 2018 ; Khan et al, 2019 ; Bitarafan et al, 2020 ; Kannan-Sundhari et al, 2020 ; Zhou et al, 2020 ; Table 1 ).…”

Section: Effects Of Gipc3 Mutations On the Auditor...mentioning

confidence: 99%

A review of the mechanisms underlying the role of the GIPC3 gene in hereditary deafness

Shi

Wang

2023

Front. Synaptic Neurosci.

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The GAIP interacting protein c terminus (GIPC) genes encode a small family of proteins characterized by centrally located PDZ domains. GIPC3 encodes a 312 amino acid protein. Variants of human GIPC3 are associated with non-syndromic hearing loss. GIPC3 is one of over a hundred different genes with variants causing human deafness. Screening for variants of GIPC3 is essential for early detection of hearing loss in children and eventually treatment of deafness. Accordingly, this paper assesses the status of research developments on the role of GIPC3 in hereditary deafness and the effects of pathogenic variants on the auditory system.

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Section: Effects Of Gipc3 Mutations On the Auditor...mentioning

confidence: 99%

A review of the mechanisms underlying the role of the GIPC3 gene in hereditary deafness

Shi

Wang

2023

Front. Synaptic Neurosci.

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“…Although more than 500 genes are predicted to be responsible for the function faultlessly of the auditory system, only 180 genes causing HL have been identi ed, to date (Ajam-Hossieni et al, 2022). Genetic factors account for almost half of the reports related to hearing impairment, and more than two-thirds of these cases appear as a single symptom and without any other defect under the name of non-syndromic hearing loss (NSHL) (Bitarafan et al, 2020). About 80% of NSHL is inherited in autosomal recessive, while approximately one-fth of cases are autosomal dominant.…”

Section: Introductionmentioning

confidence: 99%

Identification of novel gene variants causing autosomal recessive non-syndromic hearing loss in Iranian families

Ajam-Hosseini,

Parvini,

Angaji

2024

Preprint

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Background Hearing loss (HL) is known as the most common sensory disorder in humans, with an incidence in 466 million people worldwide. This disorder is genetically highly heterogeneous, so that among the 180 genes responsible for HL, a disproportionate share of genes is involved in different ethnicities. Here, we report the underlying genetic cause of non-syndromic hearing loss (NSHL) segregating in four Iranian unrelated families. Methods In the first step, patients were examined for mutations in the common genes GJB2 and GJB6. After confirming the negativity of mutations in these genes, the affected patients were subjected to targeted exome sequencing (TES). Subsequently, Sanger sequencing was used to confirm the mutations found in the patients and their family members. In silico analyses were used to consider the possible deleterious effect of the identified variants on encoded proteins. Results TES revealed a novel intronic mutation c.490-8C > A in CABP2 gene, a novel ~ 154 kb deletion mutation including OTOA gene involved in HL, and two previously reported mutations c.413C > A and c.966dupC in TMPRSS3 and COL11A2 genes, respectively. In addition, segregation analysis and in-silico evaluations confirmed the disease-causing nature of mutations found. Conclusion Our findings could extend the pathogenic mutations spectrum of NSHL, highlight the high genetic heterogeneity of HL and also aid to conduct genetic counseling, prenatal diagnosis and clinical management of HL in the Iranian population.

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“…It is estimated that congenital hearing loss affects 1-2 per 1000 individuals of the Western population while in the Iranian population it reaches one in 166, making it the second most common disorder after intellectual disability (6). This relatively high frequency of HL may be described by a high rate of consanguineous marriages, 38% on average, among the Iranian population because of several factors like their culture, tradition, and religion (7). Studies showed that more than two-thirds of congenital hearing loss is caused by genetic factors (8).…”

Section: Introductionmentioning

confidence: 99%

Identification of GJB2 Variants in 75 Unrelated Iranian Autosomal Recessive Non-syndromic Hearing Loss Patients

et al. 2022

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Background: Hearing loss (HL) is the most prevalent sensory disease in humans. HL is among the most clinically and genetically heterogeneous disorders. Pathogenic variants in GJB2 are the main cause of HL in many populations. Therefore, GJB2 analysis should be considered as the first step for HL. Objectives: This study aimed to find causative variants in the GJB2 gene in 75 unrelated Iranian patients who suffered from Autosomal recessive non-syndromic hearing loss (ARNSHL). Methods: Peripheral blood samples were used for genomic DNA extraction. PCR-direct sequencing was performed to detect GJB2 mutations. Results: In this study, thirty-four chromosomes (21.33%) carried GJB2 mutations. In total, 10 variants in 19 cases were detected. Seven cases were homozygous for c.35delG; (p.Gly12Valfs*2), two were homozygous for c.71G>A; (p.Trp24*), two were homozygous for c.358-360delGAG (p.Glu120del), and two were homozygous for c.-23+1G>A mutations. One patient was a compound heterozygote for c.35delG and c.-23+1G>A mutation, and another patient with compound heterozygosity for c.290dupA and c.235delC mutations were determined. Four patients carried a mono-allelic variant in the GJB2 including c.126G>T; (p.Glu42Asp), c.23C>T; (p.Thr8Met), c.445G>A; (p.Ala149Thr) and c.269T>C; (p.Leu90Pro). Accordingly, c.35delG mutation was the most common variant in this study. Conclusions: Finding common variants of HL mutations in different populations can elevate the diagnostic value of molecular testing in the screening of affected individuals, and can improve counselling to minimize the risk of having affected offspring for at-risk couples. Besides, early diagnosis can easily lead to speech development and prevents further problems.

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Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next‐generation sequencing

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 10 publications

References 42 publications

A review of the mechanisms underlying the role of the GIPC3 gene in hereditary deafness

A review of the mechanisms underlying the role of the GIPC3 gene in hereditary deafness

Identification of novel gene variants causing autosomal recessive non-syndromic hearing loss in Iranian families

Identification of GJB2 Variants in 75 Unrelated Iranian Autosomal Recessive Non-syndromic Hearing Loss Patients

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