Genetic analysis and prenatal diagnosis of 20 Chinese families with oculocutaneous albinism

• Published in: Journal of clinical laboratory analysis Vol. 35; no. 2; pp. e23647 - n/a
• Main Authors: Xu, Chenyang, Xiang, Yanbao, Li, Huanzheng, Xu, Yunzhi, Mao, Yijian, Zhou, Lili, Xu, Xueqin, Tang, Shaohua
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.02.2021; John Wiley and Sons Inc
• Subjects: Albinism; Deoxyribonucleic acid; DNA; Exons; Families & family life; Fetuses; Genes; Genetic analysis; Genetic counseling; Genetic disorders; Genetic screening; Genomes; Genomics; HPS1; Melanin; OCA; Patients; Polymorphism; Prenatal diagnosis; Proteins; Skin; TYR; whole exome sequencing; China; TYR; OCA; prenatal diagnosis; whole exome sequencing; HPS1
• ISSN: 0887-8013; 1098-2825
• DOI: 10.1002/jcla.23647

Background 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. Results 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). Conclusions 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. We showed the clinical phenotype and genetic diagnosis results of 20 OCA patients. A total of 21 distinct alleles, including seven novel variants, of the TYR, OCA2, and HPS1 were detected by Sanger sequencing or whole exome sequencing. This study expands our understanding of the genotypic spectrum of the Chinese OCA population and highlights that whole exome sequencing can contribute to more accurate and efficient clinical diagnoses.