一个COL11A1基因新剪接变异导致的先天性高度近视家系的遗传学分析

摘要

Objective To analyze genetic variant in a pedigree affected with congenital high myopia. Methods Whole exome sequencing (WES)was carried out for the proband.Suspected variation was verified with Sanger sequencing.The pedigree was also subjected to co-segregation analysis.Results WES has identified a novel splice site heterozygous variant (c.2556 + 1G > A)in the COL11A1 gene in the proband.Co-segregation analysis of the pedigree showed that the affected mother and two daughters of the proband have carried the same variant(c.2556 + 1G> A),while his unaffected father and sister did not. Based on the ACMG Standards and Guidelines for the Interpretation of Sequence Variants,the variant was classified as "likely pathogenic"(PVS1+PM2).Conclusion A novel splice variant (c.2556 + 1G>A)of the COL11A1 gene has been identified in a pedigree affected with congenital high myopia,which probably underlies the disease.%目的 对1个先天性高度近视家系进行基因变异分析,探讨其致病原因.方法 对先证者进行全外显子组测序,应用Sanger测序验证可疑致病变异,并进行家系共分离分析.结果 基因测序显示先证者COL11A1基因存在c.2556+1G＞A剪接位点杂合变异,家系中另3例患者(先证者母亲和两个女儿)均存在c.2556+1G＞A杂合变异,表型正常家系成员(先证者父亲、妹妹)均未发现该变异,表型与基因型在家系内共分离.经查阅OMIM、HGMD及Clinvar数据库,c.2556+1G＞A变异为未报道过的新变异.根据ACMG遗传变异分类标准与指南,c.2556+1G＞A变异符合PVS1+PM2,可以判定为可能致病性变异.结论 COL11A1基因c.2556+1G＞A剪接变异可能是该家系患者的致病原因,致病性变异的检出为家系的遗传咨询和产前诊断提供了依据.