A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS-based genetic diagnosis.
A novel, homozygous nonsense variant of the CDHR1 gene in a Chinese family causes autosomal recessive retinal dystrophy by NGS-based genetic diagnosis.
复制标题
通过基于 NGS 的基因诊断，一个中国家族中 CDHR1 基因的新型纯合无义变异导致常染色体隐性遗传性视网膜营养不良。
DOI：
10.1111/jcmm.13841
复制
发表时间：
2018-11
影响因子：
5.3
通讯作者：
Fu J
中科院分区：
文献类型：
--
作者：
Fu J;Ma L;Cheng J;Yang L;Wei C;Fu S;Lv H;Chen R;Fu J
视网膜营养不良是一种遗传性、异质性、慢性和进行性的视觉功能障碍。在中国人群中，尚未充分描述常染色体隐性视网膜病变锥杆功能障碍和黄斑营养不良患者的突变。在这项研究中，招募了一个三代中国视网膜营养不良家族。进行眼科检查。靶向下一代测序（TGS）用于鉴定致病基因，并进行桑格测序以验证候选突变和共分离。应用逆转录-PCR技术研究cdhr 1基因在小鼠体内的时空表达模式。在常染色体隐性视网膜营养不良家族中发现了CDHR 1基因中的一种新型纯合、有害和无义变体（c.T1641A; p.Y547*），该变体与该家族的临床表型共分离。RT-PCR分析显示，cdhr 1在眼睛中普遍表达，特别是在视网膜中非常高的表达;在透镜、巩膜和角膜中高表达;以及在脑中高表达。总之，我们的研究是第一个表明CHDR 1基因中的新型纯合变体c.T1641A（p.Y547*）可能是我们患者视网膜营养不良的致病突变，扩展了其突变谱。这些发现进一步了解这种疾病的分子发病机制，并提供新的见解诊断以及遗传咨询的新含义。
Retinal dystrophy is an inherited, heterogeneous, chronic and progressive disorder of visual functions. The mutations of patients with autosomal recessive retinal retinopathy cone‐and‐rod dysfunction and macular dystrophy have not been well described in the Chinese population. In this study, a three‐generation Chinese retinal dystrophy family was recruited. Ophthalmic examinations were performed. Targeted next generation sequencing (TGS) was used to identify causative genes, and Sanger sequencing was conducted to verify candidate mutations and co‐segregation. Reverse transcription (RT)‐PCR was applied to investigate the spatial and temporal expression patterns of cdhr1 gene in mouse. A novel, homozygous, deleterious and nonsense variant (c.T1641A; p.Y547*) in the CDHR1 gene was identified in the family with autosomal recessive retinal dystrophy, which was co‐segregated with the clinical phenotypes in this family. RT‐PCR analysis revealed that cdhr1 is ubiquitously expressed in eye, particularly very high expression in retina; high expression in lens, sclera, and cornea; and high expression in brain. In conclusion, our study is the first to indicate that the novel homozygous variant c.T1641A (p.Y547*) in the CHDR1 gene might be the disease‐causing mutation for retinal dystrophy in our patient, extending its mutation spectrums. These findings further the understanding of the molecular pathogenesis of this disease and provide new insights for diagnosis as well as new implications for genetic counselling.
登录
查看更多内容
影响因子：
4.6
作者：
Nikopoulos K;Avila-Fernandez A;Corton M;Lopez-Molina MI;Perez-Carro R;Bontadelli L;Di Gioia SA;Zurita O;Garcia-Sandoval B;Rivolta C;Ayuso C
通讯作者：
Ayuso C
影响因子：
16.2
作者：
Rattner, A;Smallwood, PM;Nathans, J
通讯作者：
Nathans, J
DOI：
10.1161/circgenetics.108.829747
发表时间：
2009-02
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Psaty BM;O'Donnell CJ;Gudnason V;Lunetta KL;Folsom AR;Rotter JI;Uitterlinden AG;Harris TB;Witteman JC;Boerwinkle E;CHARGE Consortium
通讯作者：
CHARGE Consortium
影响因子：
5.3
作者：
Hu P;Wu S;Yuan L;Lin Q;Zheng W;Xia H;Xu H;Guan L;Deng H
通讯作者：
Deng H
TWIST 通过在乳腺癌细胞中募集 NuRD 蛋白复合物来抑制雌激素受体 α 的表达。
影响因子：
9.2
作者：
Fu J;Zhang L;He T;Xiao X;Liu X;Wang L;Yang L;Yang M;Zhang T;Chen R;Xu J
通讯作者：
Xu J