摘要目的:观察并确定1个 NDP基因突变家系的基因变异位点和临床表型，同时为子代的产前诊断提供依据。 方法:家系调查研究。2019年7月至2021年12月于甘肃省妇幼保健院就诊的 NDP基因突变的一个3代汉族家系的2例患者和6名家系成员纳入研究。患者及其父母行瞳孔对光反射、带状光检影、视力评估、眼底彩色照相、广角荧光素眼底血管造影（FFA）检查。采集所有受检者外周血，行全外显子组测序筛选致病基因，多重连接探针扩增检测 NDP基因。先证者母亲第3次妊娠19周时经羊水穿刺行DNA产前诊断。 结果:先证者（Ⅲ1），男，4岁，足月顺产。出生40 d左右时B型超声检查提示双眼视网膜全脱离。听力、智力正常。未行眼底检查。先证者第1同胞（Ⅲ2，大弟），出生30 d眼科检查，双眼视网膜脱离。先证者母亲（Ⅱ2），双眼颞侧周边视网膜未血管化；广角FFA检查，双眼颞侧周边视网膜未血管化，末梢血管荧光素轻度渗漏。先证者第2同胞（Ⅲ3，小弟），出生后1 d于行新生儿眼病筛查。双眼外眼未见异常；角膜、晶状体透明；双眼视盘、黄斑未见异常，周边视网膜血管化，未见血管纡曲。基因检测结果显示，先证者（Ⅲ1）及其大弟（Ⅲ2） NDP基因的第2号外显子存在半合子缺失；其母亲（Ⅱ2） NDP基因第2号外显子存在杂合缺失。先证者母亲再次生育时产前诊断未检测到与先证者相同的 NDP基因第2号外显子缺失变异。先证者父亲（Ⅱ1）、舅舅（Ⅱ3）、外祖父（Ⅰ1）、外祖母（Ⅰ2）表型及基因检测结果均未见异常。 结论:NDP基因的第2号外显子存在的半合子缺失为本家系的致病变异；不同性别者其临床表型各异；产前诊断是有效阻断家族遗传疾病的方式。

abstractsObjective:To observe and determine the gene mutation site and clinical phenotype of a NDP gene mutant family, and provide a basis for the prenatal diagnosis of offspring. Methods:A pedigree investigation study. Two patients and 6 family members of a third-generation Han family with NDP gene mutation who were admitted to the Maternal and Child Health Hospital of Gansu Province from July 2019 to December 2021 were included in the study. The patients and their parents underwent the examination of pupil light reflex, strip light imaging, visual acuity evaluation, fundus color photography, and wide-field fluorescein fundus angiography (FFA). Peripheral blood of all the subjects was collected, the pathogenic genes were screened by whole exome sequencing, and NDP genes were detected by amplification of multiple ligated probes. DNA prenatal diagnosis was performed by amniocentesis at 19th weeks of the mother's third gestation. Results:Proband (Ⅲ1), male, 4 years old, full term natural delivery. At about 40 days after birth, B-mode ultrasonography indicated total retinal detachment in both eyes. Normal hearing and intelligence. Fundus examination was not performed. First sibling of proband (Ⅲ2, big younger brother), ophthalmologic examination 30 days after birth, retinal detachment in both eyes. Proband's mother (Ⅱ2) had unvascularized peripheral temporal retina in both eyes. Wide-angle FFA examination showed no vascularization of the peripheral temporal retina in both eyes, and slight leakage of peripheral vascular fluorescein. The proband's second sibling (Ⅲ3, little younger brother) was screened for neonatal eye disease 1 day after birth. No abnormalities were observed outside both eyes. Cornea and lens transparent. No abnormalities were observed in the optic disc and macula in both eyes. No vascular curvature was observed in the peripheral retina. The results of gene detection showed that there was hemizygote deletion in exon 2 of NDP gene of the proband (Ⅲ1) and its big younger brother (Ⅲ2). His mother (Ⅱ2) had heterozygosity deletion in exon 2 of NDP gene. The phenotype and genetic test results of the proband's father (Ⅱ1), uncle (Ⅱ3), maternal grandfather (Ⅰ1) and maternal grandmother (Ⅰ2) were not abnormal. Conclusions:The hemizygote deletion in exon 2 of NDP gene is a pathogenic variation in the native family. The clinical phenotypes of different genders are different. Prenatal diagnosis is an effective way to block hereditary diseases in families.