Targeted Next-Generation Sequencing Successfully Detects Causative Genes in Chinese Patients with Hereditary Hearing Loss.
OBJECTIVE
We attempted to identify the genetic epidemiology of hereditary hearing loss among the Chinese Han population using next-generation sequencing (NGS).


METHODS
The entire length of the genes GJB2, SLC26A4, and GJB3, as well as exons of 57 additional candidate genes were sequenced from 116 individuals suffering from hearing loss.


RESULTS
Thirty potentially causative mutations from these 60 genes were identified as the likely etiologies of hearing loss in 67 of the cases. In our study, SLC26A4 and GJB2 were the most frequently affected genes among the Chinese Han population with hearing loss. Collectively, they account for 52.8% of the cases, followed by MTRNR1, PCDH15, and TECTA. These data also illustrate that NGS can be used to identify rare alleles responsible for hereditary hearing loss: 22 of the 30 (73.3%) genes identified with mutations are rarely mutated in hereditary hearing loss and only account for 21.5% (42/195) of the total mutation frequency, explaining no more than 2% for each gene. These rarely mutated genes would be missed by conventional diagnostic sequencing approaches.


CONCLUSIONS
NGS can be used effectively to identify both the common and rare genes causing hereditary hearing loss.
1 Department of Otolaryngology Head and Neck Surgery, Peking University First Hospital , Beijing, China .
Siqi
S
Chen
1 Department of Otolaryngology Head and Neck Surgery, Peking University First Hospital , Beijing, China .
Cheng
C
Dong
1 Department of Otolaryngology Head and Neck Surgery, Peking University First Hospital , Beijing, China .
Qi
Q
Wang
1 Department of Otolaryngology Head and Neck Surgery, Peking University First Hospital , Beijing, China .
Zhen
Z
Zhong
2 Laboratory Center, Peking University First Hospital , Beijing, China .
Yu
Y
Qi
1 Department of Otolaryngology Head and Neck Surgery, Peking University First Hospital , Beijing, China .
Xiaomei
X
Ke
1 Department of Otolaryngology Head and Neck Surgery, Peking University First Hospital , Beijing, China .
Yuhe
Y
Liu
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D003638:Deafness / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005091:Exons; D005260:Female; D034381:Hearing Loss / Q000453:epidemiology / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D000076988:Sulfate Transporters; D055815:Young Adult
D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26
NGS; deafness; genes; hearing loss; mutation