Novel compound heterozygous EYS variants may be associated with arRP in a large Chinese pedigree
Novel compound heterozygous EYS variants may be associated with arRP in a large Chinese pedigree
复制标题
DOI：
10.1042/bsr20193443
复制
发表时间：
2020-05
影响因子：
4
通讯作者：
Chunli Wei;Ting Xiao;Jingliang Cheng;Jiewen Fu;Qi Zhou;Lisha Yang;H. Lv;Junjiang Fu
中科院分区：
文献类型：
--
作者：
Chunli Wei;Ting Xiao;Jingliang Cheng;Jiewen Fu;Qi Zhou;Lisha Yang;H. Lv;Junjiang Fu
摘要作为一种遗传性异质性眼营养不良，常染色体隐性遗传性视网膜色素变性(Arrp)患者的基因突变尚未得到很好的描述。我们的目的是检测一个中国人arrp家系的致病基因和变异。在本研究中，招募了一个由31名成员组成的中国家系，其中包括一名先证者和另外两名患者；进行临床检查；使用基因面板进行下一代测序来鉴定致病基因，并进行Sanger测序来验证突变。发现了与临床rp表型共分离的新型EYS基因复合杂合体c.G2504A(p.C835Y)和c.G6557A(p.G2186E)。对100名种族匹配的正常对照组进行测序后，没有在眼睛中发现这些突变。因此，我们的研究确定了在这个中国家庭中可能导致ARRP的EYS致病变异。这是首次发现EYS基因(c.G2504A，p.C835Y)的新突变，扩大了其突变谱。因此，EYSC.G2504A(p.C835Y)和c.G6557A(p.G2186E)变异可能是这个ARRP大家族中致病的RP错义突变。这些发现将有助于arrp病的分子诊断、遗传咨询和临床治疗。
Abstract As a genetically heterogeneous ocular dystrophy, gene mutations with autosomal recessive retinitis pigmentosa (arRP) in patients have not been well described. We aimed to detect the disease-causing genes and variants in a Chinese arRP family. In the present study, a large Chinese pedigree consisting of 31 members including a proband and another two patients was recruited; clinical examinations were conducted; next-generation sequencing using a gene panel was used for identifying pathogenic genes, and Sanger sequencing was performed for verification of mutations. Novel compound heterozygous variants c.G2504A (p.C835Y) and c.G6557A (p.G2186E) for the EYS gene were identified, which co-segregated with the clinical RP phenotypes. Sequencing of 100 ethnically matched normal controls didn’t found these mutations in EYS. Therefore, our study identified pathogenic variants in EYS that may cause arRP in this Chinese family. This is the first study to reveal the novel mutation in the EYS gene (c.G2504A, p.C835Y), extending its mutation spectrum. Thus, the EYS c.G2504A (p.C835Y) and c.G6557A (p.G2186E) variants may be the disease-causing missense mutations for RP in this large arRP family. These findings should be helpful for molecular diagnosis, genetic counseling and clinical management of arRP disease.