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  

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

作　　者：李洪义[1] 魏海云[1] 郑辉[2] 孟舒[1] 蒋玮莹[1] 陈路明[1] 段红蕾[3] 

机构地区：[1]中山大学中山医学院医学遗传学研究室,广州510080 [2]暨南大学医学院分子生理学研究室 [3]南京市鼓楼医院妇产科遗传室

出　　处：《中华医学杂志》2007年第16期1123-1125,共3页National Medical Journal of China

基　　金：广东省自然科学基金(04009328);广东省医学科研基金(A2005345)

摘　　要：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 TYR 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。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.

关 键 词：白化病 眼皮肤 产前诊断 突变 P基因 

分 类 号：R714.5[医药卫生—妇产科学]