Jia Xiuhua, Yuan Jin, Jia Xiaoyun, Ling Shiqi, Li Shiqiang, Guo Xiangming
Department of Ophthalmology, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China.
Mol Med Rep. 2017 May;15(5):3069-3075. doi: 10.3892/mmr.2017.6366. Epub 2017 Mar 23.
The aim of the present study was to evaluate mutations of the G protein-coupled receptor 143 (GPR143) gene for ocular albinism type 1 (OA1) in Chinese patients. For the current study, 8 patients with OA1 were selected from the database of ocular genetic diseases. Genomic DNA of OA1 was prepared from venous leukocytes collected from the patients. Cycle sequencing was used to analyze the exons and adjacent introns of GPR143. The variation detected was analyzed by bidirectional DNA sequencing and further evaluated in 96 controls using heteroduplex‑single strand conformational polymorphism analysis. Additionally, slit lamp photography of anterior segment, fundus photography and optical coherence tomography (OCT) were performed to identify the clinical features of OA1. In five patients with OA1, 5 GPR143 gene mutations were identified and four of them there were novel mutations. The screening rate is 62.5%, including c.333G>A (p.W111X), c.353G>A (p.G118E) (known mutation), C.658+2T>G (splice mutation), c.215_216insCGCTGC (p.71‑72insAA) and c.17T>C (p. L6P). These mutations were absent in the 96 normal controls. Only one patient with OA1 in the present study was female. Patients with OA1 often have congenital nystagmus, refractive error, severe decline of visual acuity (from 0.1 to 0.4) and foveal hypoplasia. Different degrees of pigment loss were evident in the patients' iris and retina, whereas macular structure was not identified in the OCT examination. The findings of the present study expanded the gene mutation spectrum of GPR143 and investigated the clinical phenotype of patients with OA1 in the Chinese population. Additional evidence for clinical diagnosis was provided along with differential diagnosis and genetic counseling.
本研究的目的是评估中国患者中1型眼白化病（OA1）的G蛋白偶联受体143（GPR143）基因突变情况。在本次研究中，从眼部遗传疾病数据库中选取了8例OA1患者。OA1的基因组DNA由采集自患者的静脉白细胞制备而成。采用循环测序法分析GPR143的外显子和相邻内含子。通过双向DNA测序分析检测到的变异，并使用异源双链 - 单链构象多态性分析在96名对照中进一步评估。此外，进行了眼前节裂隙灯照相、眼底照相和光学相干断层扫描（OCT）以确定OA1的临床特征。在5例OA1患者中，鉴定出5个GPR143基因突变，其中4个为新突变。筛查率为62.5%，包括c.333G>A（p.W111X）、c.353G>A（p.G118E）（已知突变）、C.658+2T>G（剪接突变）、c.215_216insCGCTGC（p.71 - 72insAA）和c.17T>C（p.L6P）。这些突变在96名正常对照中未出现。本研究中只有1例OA1患者为女性。OA1患者常伴有先天性眼球震颤、屈光不正、视力严重下降（从0.1至0.4）和黄斑发育不全。患者的虹膜和视网膜有不同程度的色素脱失，而在OCT检查中未发现黄斑结构。本研究结果扩展了GPR143的基因突变谱，并调查了中国人群中OA1患者的临床表型。为临床诊断、鉴别诊断和遗传咨询提供了额外证据。
