A novel homozygous variant of GPR98 causes usher syndrome type IIC in a consanguineous Chinese family by next generation sequencing.
A novel homozygous variant of GPR98 causes usher syndrome type IIC in a consanguineous Chinese family by next generation sequencing.
复制标题
通过下一代测序发现 GPR98 的新型纯合变异在中国近亲家庭中导致 IIC 型引座综合征
DOI：
10.1186/s12881-018-0602-0
复制
发表时间：
2018-06-11
影响因子：
--
通讯作者：
Fu J
中科院分区：
文献类型：
--
作者：
Wei C;Yang L;Cheng J;Imani S;Fu S;Lv H;Li Y;Chen R;Leung EL;Fu J
背景Usher综合征（USH）是一种常见的异质性视网膜病变和听力损失（HL）综合征。然而，基因引起的Usher综合征IIC型（USH 2C）在一个血缘中国pedigree.MethodsWe进行了有针对性的下一代测序分析和桑格测序探讨GPR 98突变USH 2C家系，其中包括一个32岁的男性患者从一个血缘婚姻家庭。Western blot验证了无义突变。ResultsTo鉴定致病基因变异在一个中国血缘家系USH 2C，先证者的DNA进行了分析，使用靶向下一代测序（NGS）。通过全面的听觉和眼科评估，患者在临床上被记录为可能的USH 2。我们成功地鉴定了GPR 98基因（NM_032119. 3）中的有害的、新的和同源的变体c.6912dupG（p.Leu2305Valfs*4），该变体有助于USH 2C的进展。然后确认通过靶向NGS检测到的变体，并通过直接桑格测序进行共分离。Western blot证实GPR 98缺失了近三分之二的氨基酸残基，包括部分Calx-β、完整的EPTP和C端的7 TM-GPCR。此外，我们的研究结果强调，这种p.Leu2305Valfs*4变体最有可能是致病性的，因为GPR 98蛋白中的七跨膜G蛋白偶联受体（7 TM-GPCR）结构域存在大的缺失，导致功能和复合物稳定性显著降低。
BackgroundUsher syndrome (USH) is a common heterogeneous retinopathy and a hearing loss (HL) syndrome. However, the gene causing Usher syndrome type IIC (USH2C) in a consanguineous Chinese pedigree is unknown.MethodsWe performed targeted next-generation sequencing analysis and Sanger sequencing to explore the GPR98 mutations in a USH2C pedigree that included a 32-year-old male patient from a consanguineous marriage family. Western blot verified the nonsense mutation.ResultsTo identify disease-causing gene variants in a consanguineous Chinese pedigree with USH2C, DNA from proband was analyzed using targeted next generation sequencing (NGS). The patient was clinically documented as a possible USH2 by a comprehensive auditory and ophthalmology evaluation. We succeeded in identifying the deleterious, novel, and homologous variant, c.6912dupG (p.Leu2305Valfs*4), in the GPR98 gene (NM_032119.3) that contributes to the progression of USH2C. Variant detected by targeted NGS was then confirmed and co-segregation was conducted by direct Sanger sequencing. Western blot verified losing almost two-thirds of its amino acid residues, including partial Calx-beta, whole EPTP and 7TM-GPCRs at the C-terminus of GPR98. Furthermore, our results highlighted that this p.Leu2305Valfs*4 variant is most likely pathogenic due to a large deletion at the seven-transmembrane G protein-coupled receptors (7TM-GPCRs) domain in GPR98 protein, leading to significantly decreased functionality and complex stability.Conclusions
登录
查看更多内容
影响因子：
2.1
作者：
Hartel, Bas P.;van Nierop, Josephine W. I.;Pennings, Ronald J. E.
通讯作者：
Pennings, Ronald J. E.
影响因子：
4.4
作者：
Jaijo, Teresa;Aller, Elena;Millan, Jose M.
通讯作者：
Millan, Jose M.
DOI：
10.1159/000016167
发表时间：
1998-01-01
期刊：
Community genetics
影响因子：
--
作者：
Espinos, C;Millan, J M;Najera, C
通讯作者：
Najera, C
影响因子：
4.8
作者：
Chen, Qian;Zou, Junhuang;Yang, Jun
通讯作者：
Yang, Jun
影响因子：
4
作者：
Ebermann, I.;Wiesen, M. H. J.;Bolz, H. J.
通讯作者：
Bolz, H. J.