眼皮肤白化病Ⅱ型产前基因诊断研究及二种P基因新突变

目的对1例眼皮肤白化病（OCA）患儿进行基于DNA的分型诊断,并在此基础上进行OCA产前基因诊断。方法应用PCR技术、DNA序列测定技术和变性高效液相层析（DHPLC）技术,分析患儿及其父母的OCA相关基因,确定患儿的分型诊断和基因型后,于其母孕20周时取羊水,以DNA序列测定技术进行OCA产前基因诊断。结果先证者’rYR基因未见突变,1对P基因分别存在N476D和Y827H突变。群体中100名表型正常者中未见此2种突变等位基因。胎儿获得了母源性N476D突变,未获得父源性Y827H突变,推测胎儿为表型正常的致病基因携带者。胎儿出生后表型正常,与产前基因诊断结果相符。结论成功开展了1例OCA2产前基因诊断并发现2种致病性P基因新突变N476D和Y827H,对今后开展该病的基础研究和预防与优生工作具有重要意义。

Prenatal diagnosis of oculocutaneous albinism type II and discovery of two novel mutations

OBJECTIVE: To investigate the genotype of oculocutaneous albinism type II (OCA2) and perform prenatal gene diagnosis for OCA2. METHODS: Peripheral blood samples were collected from a 9-year-old girl with OCA and her parents, the mother being pregnant. PCR, automatic sequence analysis and denaturing high performance liquid chromatography (DHPLC) were used to analyze the TYR gene and P gene so as to screen the OCA genes. Amniocentesis was conducted when the mother was 20-week pregnant and the amniotic cells underwent screening of the 2 specific mutations. Peripheral blood samples were collected from 100 healthy persons without phenotype of OCA to undergo genetic analysis. RESULTS: The TYR gene of the proband did not show any mutation, and 2 new mutations were found in her P gene: p. N476D (c. 1426 A>G) and p.Y827H (c.2479T>C). Her father and mother were heterozygote of Y827H and N476D respectively. Based on these findings the amniotic cells underwent sequencing of enlarged fragments of the exons 14 and 24 containing the mutation sites. The result showed that the fetus only got the maternal N476D mutation and didn't get the paternal Y827H mutation. So the fetus was predicted to be a carrier of OCA2 with normal appearance. The baby was born normal later as predicted. None of these 2 mutations was found in the 100 healthy persons. CONCLUSION: This is a success of prenatal gene diagnosis of OCA2. Two novel mutations of the P gene related to OCA have been discovered.