Spectrum of pathological genetic variants among 405 Chinese pedigrees affected with oculocutaneous albinism.
10.3760/cma.j.issn.1003-9406.2020.07.006
- VernacularTitle:中国大陆地区405例眼皮肤白化病家系的致病基因变异谱研究
- Author:
Conghui WANG
1
;
Chen CHEN
;
Xuechao ZHAO
;
Ganye ZHAO
;
Lina LIU
;
Xiangdong KONG
Author Information
1. Genetics and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. kongxdtougao@163.com.
- Publication Type:Journal Article
- From:
Chinese Journal of Medical Genetics
2020;37(7):725-730
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To determine the spectrum of pathological genetic variants among 405 Chinese pedigrees affected with oculocutaneous albinism (OCA).
METHODS:A total of 405 OCA patients were collected. High-throughput sequencing (The panel included TYR, OCA2, TYRP1 and SLC45A2 genes), Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) were used to analyze the genetic variants and patterns of each subtype.
RESULTS:The overall detection rate of genetic variants was 79.9% (647/810), and the variants included missense variants (57.3%, 371/647), frameshift variants (22.9%, 148/647), nonsense variants (13.9%, 90/647), splicing variants (5.6%, 36/647), and microdeletions (0.3%, 2/647). Thirty-six novel variants were detected. Of the 405 patients, 306 have carried 2 variant alleles (75.6%, 306/405), 35 carried 1 variant alleles (8.6%, 35/405), while no variant was detected in 64 patients. Among the 306 genetically diagnosed OCA patients, OCA1 was the most common form (74.5%, 228/306), compared with OCA2 (15.0%, 46/306), OCA3 (0.7%, 2/306) and OCA4 (9.8%, 30/306), respectively. One patient was found to harbor homozygous c.1262-4_c.1262-3insTAGA variant of the TYRP1 gene. Another patient was found to carry compound heterozygous variants of c.1214C>A (p.T405N) and c.1338delinsCG(p.V447Gfs*19) of the TYRP1 gene.
CONCLUSION:High-throughput sequencing in combination with Sanger sequencing and MLPA can effectively detect genetic variants associated with OCA. Above finding has expanded variant spectrum of OCA, which can facilitate genetic and prenatal diagnosis of this disease in China.
