Liu Ning, Kong Xiang Dong, Shi Hui Rong, Wu Qing Hua, Jiang Miao
Prenatal Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,P. R. China.
Genet Res (Camb). 2014 Nov 12;96:e14. doi: 10.1017/S0016672314000160.
Oculocutaneous albinism (OCA) is a heterogeneous autosomal recessive genetic disorder that affects melanin synthesis. OCA results in reduced or absent pigmentation in the hair, skin and eyes. Type 1 OCA (OCA1) is the result of tyrosinase (TYR) gene mutations and is a severe disease type. This study investigated TYR mutations in a Chinese cohort with OCA1. This study included two parts: patient genetic study and prenatal genetic diagnosis. A total of 30 OCA1 patients were subjected to TYR gene mutation analysis. Ten pedigrees were included for prenatal genetic diagnosis. A total of 100 unrelated healthy Chinese individuals were genotyped for controls. The coding sequence and the intron/exon junctions of TYR were analysed by bidirectional DNA sequencing. In this study, 20 mutations were identified, four of which were novel. Of these 30 OCA1 patients, 25 patients were TYR compound heterozygous; two patients carried homozygous TYR mutations; and three were heterozygous. Among the ten prenatally genotyped fetuses, three fetuses carried compound heterozygous mutations and seven carried no mutation or only one mutant allele of TYR and appeared normal at birth. In conclusion, we identified four novel TYR mutations and showed that molecular-based prenatal screening to detect TYR mutations in a fetus at risk for OCA1 provided essential information for genetic counselling of couples at risk.
眼皮肤白化病(OCA)是一种影响黑色素合成的常染色体隐性遗传异质性疾病。OCA导致头发、皮肤和眼睛色素沉着减少或缺失。1型OCA(OCA1)是酪氨酸酶(TYR)基因突变的结果,是一种严重的疾病类型。本研究调查了一个中国OCA1队列中的TYR突变。本研究包括两个部分:患者基因研究和产前基因诊断。共有30例OCA1患者接受了TYR基因突变分析。纳入10个家系进行产前基因诊断。共有100名无亲缘关系的健康中国个体进行基因分型作为对照。通过双向DNA测序分析TYR的编码序列和内含子/外显子连接区。在本研究中,共鉴定出20个突变,其中4个为新突变。在这30例OCA1患者中,25例患者为TYR复合杂合子;2例患者携带TYR纯合突变;3例为杂合子。在10例进行产前基因分型的胎儿中,3例胎儿携带复合杂合突变,7例未携带突变或仅携带一个TYR突变等位基因,出生时表现正常。总之,我们鉴定出4个新的TYR突变,并表明基于分子的产前筛查以检测OCA1风险胎儿中的TYR突变为有风险的夫妇提供了遗传咨询的重要信息。