A novel missense mutation p.L76P in the GJB2 gene causing nonsyndromic recessive deafness in a Brazilian family

Batissoco, Ana Carla; Auricchio, Maria Teresa B.M.; Kimura, Lilian; Tabith-Junior, A.; Mingroni-Netto, Regina Célia

doi:10.1590/s0100-879x2009000200004

Cited by 11 publications

(7 citation statements)

References 17 publications

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“…Although involving a radical structurally distinct, our variant (p.Leu60Pro), located in the same exon 7, appeared to be inducing a comparable disorganizing effect on the protein alpha helix which likely resulted in the hearing impairment observed in the four patients of our cohort and also predicted for the (p.Arg81Gln) mutation [11]. Since the first reported case of direct involvement of proline in human diseases [15], mutant proteins for this amino acid have been implicated in the etiology of number of genetic disorders including non-syndromic recessive hearing impairment [16]. For instance, different studies showed that p.Ser50Pro and p.Thr56Pro variants, both consisting of replacement of wild amino acid by proline residue in connexin 50 (Cx50, GJA8), affected the protein contribution to the lens normal survival through angular restriction of α helix or β sheet secondary structure [17,18].…”

Section: Discussionsupporting

confidence: 61%

Identification a novel pathogenic LRTOMT mutation in Mauritanian families with nonsyndromic deafness

Salame¹,

Bonnet

Moctar

et al. 2023

Eur Arch Otorhinolaryngol

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Although recessive mutations in GJB2 are the common genetic etiology of sensorineural hearing impairment (SNHI), variants in LRTOMT gene were also identified, mostly in Middle East and North African populations. Methods: Using Sanger sequencing we screened the exon 7 of LRTOMT in a cohort of 128 unrelated Mauritanian children with congenital deafness. Results: One biallelic missense mutation, predicted as pathogenic (c.179T>C;p.Leu60Pro) was found at homozygous state in four independent families. This variant, not reported before, was predicted to have a deleterious effect by SIFT (score: 0.01) and a disease-causing effect by Mutation Taster (prob: 1). Exploration of the encoded protein 3D structure revealed a disruption of an organized α helix (in the normal protein structure) to a random conformation. Early fitting of a cochlear implant seemed to improve the auditory ability of the patient carrying the biallelic variant. Conclusion: Further screening using a panel of deafness genes should provide a more comprehensive view of the heterogeneity of deafness genes underlying hearing impairment in our population.

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Section: Discussionsupporting

confidence: 61%

Identification a novel pathogenic LRTOMT mutation in Mauritanian families with nonsyndromic deafness

Salame¹,

Bonnet

Moctar

et al. 2023

Eur Arch Otorhinolaryngol

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“…In this gene the novel mutation c.598G>A (p.Gly200Arg) affects a residue in the cysteine-rich domain that is involved in the formation of intramolecular disulphide bonds [28], [29]. Although the effect of glycine on the intramolecular disulphide bond formation cannot be predicted, the mutant residue arginine may affect the proper folding of the cysteine-rich domain because of the larger size of the arginine side chain.…”

Section: Discussionmentioning

confidence: 99%

Genetic Spectrum of Autosomal Recessive Non-Syndromic Hearing Loss in Pakistani Families

et al. 2014

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The frequency of inherited bilateral autosomal recessive non-syndromic hearing loss (ARNSHL) in Pakistan is 1.6/1000 individuals. More than 50% of the families carry mutations in GJB2 while mutations in MYO15A account for about 5% of recessive deafness. In the present study a cohort of 30 ARNSHL families was initially screened for mutations in GJB2 and MYO15A. Homozygosity mapping was performed by employing whole genome single nucleotide polymorphism (SNP) genotyping in the families that did not carry mutations in GJB2 or MYO15A. Mutation analysis was performed for the known ARNSHL genes present in the homozygous regions to determine the causative mutations. This allowed the identification of a causative mutation in all the 30 families including 9 novel mutations, which were identified in 9 different families (GJB2 (c.598G>A, p.Gly200Arg); MYO15A (c.9948G>A, p.Gln3316Gln; c.3866+1G>A; c.8767C>T, p.Arg2923* and c.8222T>C, p.Phe2741Ser), TMC1 (c.362+18A>G), BSND (c.97G>C, p.Val33Leu), TMPRSS3 (c.726C>G, p.Cys242Trp) and MSRB3 (c.20T>G, p.Leu7Arg)). Furthermore, 12 recurrent mutations were detected in 21 other families. The 21 identified mutations included 10 (48%) missense changes, 4 (19%) nonsense mutations, 3 (14%) intronic mutations, 2 (9%) splice site mutations and 2 (9%) frameshift mutations. GJB2 accounted for 53% of the families, while mutations in MYO15A were the second most frequent (13%) cause of ARNSHL in these 30 families. The identification of novel as well as recurrent mutations in the present study increases the spectrum of mutations in known deafness genes which could lead to the identification of novel founder mutations and population specific mutated deafness genes causative of ARNSHL. These results provide detailed genetic information that has potential diagnostic implication in the establishment of cost-efficient allele-specific analysis of frequently occurring variants in combination with other reported mutations in Pakistani populations.

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“…Hearing loss is one of the most common of sensorineural disorders [20] . Among the various types of hearing loss, sensorineural hearing loss is caused by damage to the inner ear.…”

Section: Discussionmentioning

confidence: 99%

Genetic Analysis of Genes Related to Tight Junction Function in the Korean Population with Non-Syndromic Hearing Loss

Kim

Sagong

et al. 2014

PLoS ONE

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Tight junctions (TJs) are essential components of eukaryotic cells, and serve as paracellular barriers and zippers between adjacent tissues. TJs are critical for normal functioning of the organ of Corti, a part of the inner ear that causes loss of sensorineural hearing when damaged. To investigate the relation between genes involved in TJ function and hereditary loss of sensorineural hearing in the Korean population, we selected the TJP2 and CLDN14 genes as candidates for gene screening of 135 Korean individuals. The TJP2 gene, mutation of which causes autosomal dominant non-syndromic hearing loss (ADNSHL), lies at the DFNA51 locus on chromosome 9. The CLDN14 gene, mutation of which causes autosomal recessive non-syndromic hearing loss (ARNSHL), lies at the DFNB29 locus on chromosome 21. In the present study, we conducted genetic analyses of the TJP2 and CLDN14 genes in 87 unrelated patients with ADNSHL and 48 unrelated patients with either ARNSHL or potentially sporadic hearing loss. We identified two pathogenic variations, c.334G>A (p.A112T) and c.3562A>G (p.T1188A), and ten single nucleotide polymorphisms (SNPs) in the TJP2 gene. We found eight non-pathogenic variations in the CLDN14 gene. These findings indicate that, whereas mutation of the TJP2 gene might cause ADNSHL, CLDN14 is not a major causative gene for ARNSHL in the Korean population studied. Our findings may improve the understanding of the genetic cause of non-syndromic hearing loss in the Korean population.

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A novel missense mutation p.L76P in the GJB2 gene causing nonsyndromic recessive deafness in a Brazilian family

Cited by 11 publications

References 17 publications

Identification a novel pathogenic LRTOMT mutation in Mauritanian families with nonsyndromic deafness

Identification a novel pathogenic LRTOMT mutation in Mauritanian families with nonsyndromic deafness

Genetic Spectrum of Autosomal Recessive Non-Syndromic Hearing Loss in Pakistani Families

Genetic Analysis of Genes Related to Tight Junction Function in the Korean Population with Non-Syndromic Hearing Loss

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