一个中国全色盲家系 CNGB3基因新突变

目的:探讨全色盲一家系的致病基因突变。方法:采用家系调查研究方法，于2018年11月对河南省立眼科医院收集的来自河南省洛阳市的汉族全色盲一家系进行基因测序。详细采集患者的病史资料，对患者及其家系成员进行最佳矫正视力(BCVA)测定，采用裂隙灯显微镜和前置镜检查眼前节和眼底，采用客观和主觉验光法对受检者进行屈光度检查，采...

A novel mutation of CNGB3 gene in a Chinese achromatopsia family

Objective To identify the pathogenic gene mutations in a Chinese achromatopsia family.Methods A pedigree investigation was performed.A Chinese Han pedigree from Luoyang city of China was enrolled in Henan Eye Hospital in November 2018.The medical history of the patients was collected.The best corrected visual acuity(BCVA)of the families was examined.The maniafestations of the anterior segment and fundus were obtained via slit lamp biomicroscope and slit lamp lens.The diopter was determined by objective and subjective refraction.Color vision was examined by Farnsworth-Munsell Hue Test.Retinal function was evaluated by international standard electroretinogram(ERG).Retina was observed by color photography,and its structural image was obtained by spectral-domain optical coherence tomography(SD-OCT).The peripheral blood sample was collected from the proband(Ⅲ1)and her younger brother(Ⅲ2)and parents for whole blood DNA extraction,and a whole genome sequencing(WGS)was performed to identify the pathogenic genes and mutation sites,and the sequencing data was compared through disease-related databases such as the Human Genome Databases due to a negative detective result of specific hereditary eye disease enrichment panel based on targeted exome capture technology.Sanger sequencing and bioinformatics analysis was carried out with softwares.The cosegregation analysis was performed.This study protocol was approved by an Ethics Committee of Henan Eye Hospital(No.HNEECKY-2019[15])and complied with Declaration of Helsinki.Written informed consent was obtained from each subject or the guardian before any medical examination.Results This family included 2 patients and 8 members with normal phenotypes in 3 generations and showed an autosomal recessive inheritance model.Poor vision and photophobia appeared after birth in bothⅢ1 andⅢ2,and these symptoms did not deteriorate with aging.Pigmentary mottling and atrophic changes could be seen in the retinas of the patients.Reflection bands of external membrane and ellipsoid line in macula of patients were irregular on the OCT image.Color vision examination showed achromatopsia of the patients.ERG indicated that the amplitudes of a-,b-waves of scotopic 0.01,3.0,10.0 ERG and oscillatory potentials were slightly reduced,and the amplitudes of a-,b-waves of photopic ERG and wavelets of 30 Hz were seriously reduced in both eyes ofⅢ1 andⅢ2.WGS showed that heterozygous mutations of a novel mutation c.129+1G>A and a known mutation c.1285dupT of CNGB3 gene inⅢ1 andⅢ2.The mutations were confirmed by Sanger sequencing.Conclusions The compound heterozygous mutation in c.129+1G>A/c.1285dupT of CNGB3 gene may be responsible for the achromatopsia pathogenesis in this Chinese Han pedigree.The abnormal phenotype of the patients is the result of both CNGB3 c.129+1G>A and CNGB3 c.1285dupT mutations simultaneously.