三例Menkes病患儿的家系及基因变异分析

目的:对3例Menkes病患儿家系的 ATP7A基因进行变异分析，明确其致病原因，为临床诊断提供依据。 方法:应用二代测序(next-generation sequencing，NGS)对3个Menkes病家系的先证者进行Menkes病相关致病基因 ATP7A基因外显子检测，发现可疑致...

Pedigree and ATP7A variant analysis of three children with Menkes disease

Objective To explore the genetic basis for three children with Menkes disease.Methods The patients were subjected to next-generation sequencing(NGS)to detect potential variants of the ATP7A gene.Suspected variants were verified by Sanger sequencing of their family members and 200 healthy individuals.Multiplex ligation-dependent probe amplification(MLPA)was also carried out to detect potential deletions in their family members and 20 healthy individuals.Results Variants of the ATP7A gene were detected in all of the three families,including a novel c.1465A>T nonsense variant in family 1,a novel c.3039_3043del frameshifting variant in family 2,and deletion of exons 3 to 23 in family 3,which was reported previously.Based on the American College of Medical Genetics and Genomics standards and guidelines,the c.1465A>T and c.3039_3043del variants of ATP7A gene were predicted to be likely pathogenic(PVS1+PM2).Conclusion Variants of the ATP7A gene may underlay the Menkes disease in the three children.Above findings have facilitated clinical diagnosis and enriched the gene variant spectrum of Menkes disease.