The anticipation and inheritance pattern of c.487A>G mutation in the GJB2 gene.
Mutations in the GJB2 gene are the most common causes of hereditary hearing loss. This study reveals some facts about the inheritance pattern of M163V in the GJB2 gene. This study was performed on two different families with non-syndromic hearing loss. We screened the GJB2 coding region with direct sequencing. There was a substitution of A to G in exon 2 at nucleotide 487 (M163V). This mutation was heterozygous in fathers and children while mothers were normal. Fathers of both families showed late onset hearing impairment, but there was early onset hearing loss in the children, which was more severe compared to the fathers. M163V has been reported as an unknown heterozygous mutation that leads to failure of the homotypic junctional channel formation. Another mutation in this codon is M163L, with an autosomal dominant inheritance, which impairs trafficking through the plasma membrane, resulting in cell death. Assessment of the familial pedigree has revealed anticipation in phenotype and autosomal dominant inheritance. These data in addition to the high conservation of methionine residue in mammalian species suggest that M163V is inherited with an autosomal dominant pattern. Therefore, the risk of inheritance will increase. Genetic counselors and otologists should prioritize the evaluation and prevention of this disorder in patients.
Department and Research Centre of ENT and Head and Neck Surgery, Tehran University of Medical Sciences, Iran. mfa.ent@gmail.com
Masoumeh
M
Falah
Massoud
M
Houshmand
Saeid
S
Mahmoudian
Hessamalddin
H
Emamdjomeh
Yaser
Y
Ghavami
Mohammad
M
Farhadi
D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D020132:Anticipation, Genetic / Q000235:genetics*; D002648:Child; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D017629:Gap Junctions / Q000235:genetics; D005799:Genes, Dominant; D006580:Genetic Carrier Screening / Q000379:methods; D034381:Hearing Loss / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D020539:Sequence Analysis, Protein
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26