Hereditary hearing impairment is a clinically and genetically heterogeneous disease. Whole-exome sequencing was performed on seven affected and six unaffected members in a large Chinese family with autosomal-dominant nonsyndromic hearing loss. The pathogenic variant of the gene encoding human topoisomerase II beta TOP2B (c.G4837C:p.D1613H) was cosegregated with hearing loss in this pedigree and another two variants of TOP2B were detected in 66 sporadic patients with hearing loss. top2b knockdown led to significant defects in zebrafish inner ears and caused downregulation of akt which resulted in inactivation of PI3K-Akt signalling. As a result, supporting cell and hair cell numbers were reduced through inhibition of the PI3K-Akt pathway. Therefore, we hypothesized that mutations in TOP2B can cause autosomal-dominant nonsyndromic hearing impairment through inhibition of the PI3K-Akt signalling pathway. Database The whole-exome sequence data in the study are available at the Sequence Read Archive database (NCBI) under the accession numbers , , , , , , , , , , . and , respectively.
[1]Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China;
[2]Tongji Univ, Shanghai East Hosp, Dept Otorhinoiaryngoi, Shanghai 200120, Peoples R China;
[3]Fudan Univ, Dept Affiliated Eye & ENT Hosp, ENT Inst & Otorhinolaryngol, State Key Lab Med Neurobiol, Shanghai, Peoples R China;
[4]Fudan Univ, Collaborat Innovat Ctr Genet & Dev, Sch Basic Med Sci,Inst Biomed Sci, Key Lab Metab & Mol Med,Minist Educ,Dept Biochem, Shanghai, Peoples R China
(8.0+极速模式)