Open AccessA Novel GJB2 compound heterozygous mutation c.257C>G (p.T86R)/c.176del16 (p.G59A fs*18) causes sensorineural hearing loss in a Chinese family
Author(s) -
Shi Xi,
Zhang Yan,
Qiu Shiwei,
Zhuang Wei,
Yuan Na,
Sun Tiantian,
Gao Jian,
Qiao Yuehua,
Liu Ke
Publication year - 2018
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.22444
Subject(s) - compound heterozygosity , mutation , hearing loss , microbiology and biotechnology , genetics , heterozygote advantage , hek 293 cells , gene , transfection , biology , allele , medicine , audiology
Objective To investigate whether a novel compound heterozygous mutations c.257C>G (p.T86R)/c.176del16 (p.G59A fs*18) in GJB2 result in hearing loss. Methods Allele‐specific PCR‐based universal array (ASPUA) screening and sequence analysis were applied to identify these mutations. 3D model was built to perform molecular dynamics (MD) simulation to verify the susceptibility of the mutations. Furthermore, WT‐ and Mut‐ GJB2 DNA fragments, containing the mutation of c.257C>G and c.176del16 were respectively cloned and transfected into HEK293 and spiral ganglion neuron cell (SGNs) by lenti‐virus delivery system to indicate the subcellular localization of the WT‐ and Mut‐CX26 protein. Results A novel compound heterozygous mutation c.257C>G (p.T86R)/c.176del16 (p.G59A fs*18) in GJB2 was identified in a Chinese family, in which 4 siblings with profound hearing loss, but the fifth child is normal. By ASPUA screening and sequencing, a compound heterozygote mutations in GJB2 c.257C>G (p.T86R)/c.176del16 (p.G59A fs*18) were identified in these four deaf children, each of the mutated GJB2 gene were inherited from their parents. There is no mutation of GJB2 gene identified in the normal child. Besides, the compound heterozygous mutation GJB2 c.257C>G (p.T86R)/c.176del16 (p.G59A fs*18) could lead to the alterations of the subcellular localization of each corresponding mutated CX26 protein and could cause the hearing loss, which has been predicted by MD simulation and verified in both 293T and SGNs cell line. Conclusion The c.257C>G (p.T86R)/c.176del16 (p.G59A fs*18) compound mutations in GJB2 detected in this study are novel, and which may be associated with hearing loss in this Chinese family.