Key Laboratory of Birth Defects, Department of Genetics, Wenzhou Central Hospital, Wenzhou, China.
Key Laboratory of Medical Genetic, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.
J Clin Lab Anal. 2021 Feb;35(2):e23647. doi: 10.1002/jcla.23647. Epub 2020 Oct 30.
Oculocutaneous albinism (OCA) is a group of heterogeneous genetic disorders characterized by abnormal melanin synthesis in the hair, skin, and eyes. OCA exhibits obvious genetic and phenotypic heterogeneity. Molecular diagnosis of causal genes can be of help in the classification of OCA subtypes and the study of OCA pathogenesis． METHODS: In this study, Sanger sequencing and whole exome sequencing were used to genetically diagnose 20 nonconsanguineous Chinese OCA patients. In addition, prenatal diagnosis was provided to six OCA families.
Variants of TYR, OCA2, and HPS1 were detected in 85%, 10%, and 5% of affected patients, respectively. A total of 21 distinct variants of these three genes were identified. Exons 1 and 2 were the hotspot regions of the TYR variants, and c.895C > A and c.896G > A were the hotspot variants. We also found seven novel variants: c.731G > A, c.741C > A, c.867C > A, and c.1037-2A > T in TYR, c.695dupT and c.1054A > G in OCA2, and c.9C > A in HPS1. Genetic tests on six fetuses revealed three carrier fetuses, two normal fetuses, and one affected fetus. The follow-up results after birth were consistent with the results of prenatal diagnosis (one fetus terminated during pregnancy was not followed up).
This study expands our understanding of the genotypic spectrum of the Chinese OCA population. The findings indicate that prenatal diagnosis can provide important information for genetic counseling.
眼皮肤白化病（OCA）是一组以毛发、皮肤和眼睛中黑色素合成异常为特征的异质性遗传疾病。OCA 表现出明显的遗传和表型异质性。致病基因的分子诊断有助于 OCA 亚型的分类和 OCA 发病机制的研究。
本研究采用 Sanger 测序和全外显子组测序对 20 名非近亲结婚的中国 OCA 患者进行基因诊断。此外，还对 6 个 OCA 家系进行了产前诊断。
在 85%、10%和 5%的受影响患者中分别检测到 TYR、OCA2 和 HPS1 的变异。这三个基因共鉴定出 21 个不同的变异。TYR 变异的热点区域在第 1 和第 2 外显子，热点变异为 c.895C > A 和 c.896G > A。我们还发现了 7 个新的变异：c.731G > A、c.741C > A、c.867C > A 和 c.1037-2A > T 在 TYR 中，c.695dupT 和 c.1054A > G 在 OCA2 中，c.9C > A 在 HPS1 中。对 6 个胎儿进行的基因检测显示，有 3 个胎儿为携带者，2 个胎儿正常，1 个胎儿患病。出生后的随访结果与产前诊断结果一致（1 个胎儿在妊娠期间终止未进行随访）。
本研究扩展了我们对中国 OCA 人群基因型谱的认识。研究结果表明，产前诊断可为遗传咨询提供重要信息。
