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Exome Sequencing Identifies a Novel Nonsense Mutation of MYO6 as the Cause of Deafness in a Brazilian Family
Author(s) -
SampaioSilva Juliana,
Batissoco Ana Carla,
JesusSantos Rafaela,
AbathNeto Osório,
Scarpelli Luciano Cesar,
Nishimura Patricia Yoshie,
Galindo Layla Testa,
Bento Ricardo Ferreira,
Oiticica Jeanne,
Lezirovitz Karina
Publication year - 2018
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12213
Subject(s) - proband , nonsense mutation , exome sequencing , genetics , hearing loss , nonsense , mutation , biology , exome , genotype , gene , medicine , audiology , missense mutation
Summary We investigated 313 unrelated subjects who presented with hearing loss to identify the novel genetic causes of this condition in Brazil. Causative GJB2 / GJB6 mutations were found in 12.7% of the patients. Among the familial cases (100/313), four were selected for exome sequencing. In one case, two novel heterozygous variants were found and were predicted to be pathogenic based on bioinformatics tools, that is, p.Ser906* ( MYO6 ) and p.Arg42Cys ( GJB3 ). We confirmed that this nonsense MYO6 mutation segregated with deafness in this family. Only the proband and her unaffected mother exhibited the GJB3 mutation, which is in the same amino acid of a known Erythrokeratodermia variabilis mutation. None of the patients exhibited this skin disease, but the proband exhibited a more severe hearing loss. Hence, the GJB3 mutation was considered to be a variant of uncertain significance. In conclusion, we described a novel nonsense MYO6 mutation that was responsible for the hearing loss in a Brazilian family. This mutation resides in the neck domain of myosin‐VI after the motor domain. Thus, our data give further support for genotype‐phenotype correlations, which state that when the motor domain of the protein is functioning, the hearing loss is milder and has a later onset. The three remaining families without mutations in the known genes suggest that there are still deafness genes to be revealed.