摘要目的 观察分析6个白化病家系的致病基因类型及表型特征.方法 回顾性系列病例研究.6个无血缘关系家系中6例白化病先证者和20名家系成员纳入研究.6例先证者中,临床表型符合眼皮肤白化病(OCA)特征5例,符合眼白化病(OA)特征l例.采集先证者及其家系成员外周静脉血,提取全基因组DNA.运用全外显子组或Sanger测序技术进行致病基因筛查,重点分析白化病相关基因变异并分析其临床特征.结果 测序分析于4个家系中发现6个高致病突变,包括2个常染色体隐性复杂合突变[TYR(c.1037-7T＞A,c.925_c.926insC)、OCA2(c.2359G＞A,c.587T＞C)]和2个X染色体杂合突变[GPR143(c.11C＞G)、GPR143 (c.333G＞A)];其中5个为新发突变.所有突变均由Sanger测序证实,分别代表了OCA1型、OCA2型以及OA1型3种亚型.其中一家系临床表型符合OCA特征,分子遗传学证实为OA1型;其余家系临床诊断与遗传学诊断符合.结论 6个白化病家系中4个家系具有6个高致病基因突变,分别代表OCA1型、OCA2型以及OA1型3种亚型.

abstractsObjective To analyze the pathogenic gene types and phenotypic characteristics of 6 albinism families.Methods A retrospective series of case studies.Six probands of albinism and 20 family members were recruited for this study,5 probands with clinical manifestations of oculocutaneous albinism (OCA) and 1 proband of ocular albinism (OA).Genomic DNA was extracted from peripheral venous blood which was collected from 6 probands and 20 family members.Genetic variations were screened by whole-exome sequencing or Sanger sequencing and then analyzed the relationship between genotypes and phenotypes.Results Genetic sequencing identified 6 potential pathogenic variants in 4 probands,including 2 compound heterozygous mutations in the 2 genes [TYR (c.1037-7T＞A,c.925_c.926insC),OCA2 (c.2359G＞A,c.587T＞C)] associated with OCA1 and OCA2,and 2 hemizygous mutations in the GPR143[GPR143 (c.11C ＞ G),GPR 143 (c.333 G ＞ A)] as sociated with OA 1,respectively.In which,5 were novel mutations and confirmed by Sanger sequencing.One case was accorded with OCA in clinical phenotype,but genetic diagnosis was OA1,the others were agreement between clinical diagnosis and genetic diagnosis.Conclusion There are 4 families with mutations in 6 families,representative of 3 type of albinism (OCA1,OCA2,OA1).