Gu X, Guo L, Ji H, Sun S, Chai R, Wang L, Li H
Department of Otolaryngology, Hearing Research Institute, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, China.
Clin Genet. 2015 Jun;87(6):588-93. doi: 10.1111/cge.12431. Epub 2014 Aug 7.
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.
非综合征性听力损失（NSHL）的遗传异质性阻碍了其致病突变的鉴定。最近的几项研究应用靶向基因组富集（TGE）和大规模平行测序（MPS）来同时筛查大量已知的听力损失（HL）基因。然而，这些研究大多集中在家族性病例上。为了评估TGE和MPS在筛查散发性NSHL患者中的有效性，我们招募了63名无亲缘关系的散发性NSHL先证者，他们患有不同程度的HL，并且排除了GJB2、MT-RNR1和SLC26A4基因的突变。使用人类耳聋检测板oto-DA3（Otogenetics Corporation.，Norcross，GA）对131个已知的HL基因进行了TGE和MPS检测。我们在8名患者的STRC、CATSPER2、USH2A、TRIOBP、MYO15A、GPR98和TMPRSS3基因中鉴定出14个致病变异（诊断率=12.7%）。在这些变异中，有10个是新的复合杂合突变。致病突变的鉴定可以预测HL的进展，并指导该疾病的诊断和治疗。
