全基因组测序对一例无痛无汗症伴白化病患儿的基因变异分析

Analysis of genetic variation for a child affected with congenital insensitivity to pain with anhidrosis and albinism by whole genome sequencing

目的对1例无痛无汗症合并白化病患儿及其父母进行基因变异分析。方法对患儿及其父母进行全外显子组测序(whole exome sequencing,WES),在未完全找到变异位点的情况下对先证者进行了全基因组测序(whole genome sequencing,WGS),用Sanger测序对患儿及其父母的变异位点进行了验证。结果WES结果显示患儿NTRK1基因存在c.1729G>C(p.G577R)杂合错义变异,OCA2基因存在c.1363A>G(p.R455G)杂合错义变异和c.1182+1G>A内含子杂合变异。WGS另外检测到了NTRK1基因c.[851-798C>T;851-794C>G]深度内含子杂合变异。结论患儿同时患有无痛无汗症和白化病两种遗传病,分别由于NTRK1基因复合杂合变异和OCA2基因复合杂合变异引起。在WES没有检测到编码区变异位点的情况下,可以考虑应用WGS对整个基因组进行检测以期找到变异位点。

Objective To explore the genetic variation of a Chinese family affected with congenital insensitivity to pain with anhidrosis and albinism.Methods Whole exome sequencing(WES)was carried out to screen potential variants within genomic DNA extracted from the proband and his parents.Whole genome sequencing(WGS)was applied when variants were not found completely.Suspected variants were validated by Sanger sequencing.Results WES has identified a heterozygous c.1729G>C(p.G577R)variant of NTRK1 gene and two heterozygous variants of OCA2 gene,namely c.1363A>G(p.R455G)and c.1182+1G>A.WGS has identified a extra heterozygous variant c.[851-798C>T;851-794C>G]of NTRK1 gene.Conclusion The compound heterozygous variants of NTRK1 gene probably underlie the congenital insensitivity to pain with anhidrosis.And the compound heterozygous variants of OCA2 gene probably underlie the albinism.In the case that no variant is detected by WES in the coding region,we should consider using WGS to screen potential variants in the whole genome.