Genetic testing for sporadic hearing loss using targeted massively parallel sequencing identifies 10 novel mutations.
The genetic heterogeneity of non-syndromic hearing loss (NSHL) has hampered the identification of its pathogenic mutations. Several recent studies applied targeted genome enrichment (TGE) and massively parallel sequencing (MPS) to simultaneously screen a large set of known hearing loss (HL) genes. However, most of these studies were focused on familial cases. To evaluate the effectiveness of TGE and MPS on screening sporadic NSHL patients, we recruited 63 unrelated sporadic NSHL probands, who had various levels of HL and were excluded for mutations in GJB2, MT-RNR1, and SLC26A4 genes. TGE and MPS were performed on 131 known HL genes using the Human Deafness Panel oto-DA3 (Otogenetics Corporation., Norcross, GA). We identified 14 pathogenic variants in STRC, CATSPER2, USH2A, TRIOBP, MYO15A, GPR98, and TMPRSS3 genes in eight patients (diagnostic rate = 12.7%). Among these variants, 10 were novel compound heterozygous mutations. The identification of pathogenic mutations could predict the progression of HL, and guide diagnosis and treatment of the disease.
Department of Otolaryngology, Hearing Research Institute, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, China.
X
X
Gu
L
L
Guo
H
H
Ji
S
S
Sun
R
R
Chai
L
L
Wang
H
H
Li
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins; D004252:DNA Mutational Analysis; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D034381:Hearing Loss / Q000175:diagnosis* / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D055815:Young Adult
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
massively parallel sequencing; mutation screening; sporadic non-syndromic hearing loss; targeted genome enrichment