嘌呤核苷磷酸化酶缺乏症患儿1例的临床及遗传学分析

Clinical and genetic analysis of a child with purine nucleoside phosphorylase deficiency

目的本研究旨在探讨1例嘌呤核苷磷酸化酶缺乏症患儿的临床特征与遗传学病因。方法选取2021年4月至浙江大学医学院附属妇产科医院生殖遗传门诊就诊的1例嘌呤核苷磷酸化酶缺乏症患儿为研究对象。对患儿及父母进行家系全外显子组测序和生物信息学分析,并通过Sanger测序以及SNP-Array进一步验证变异。结果患儿存在PNP:c.150C>A变异和14q11.2拷贝数变异的复合杂合变异,Sanger测序和SNP-Array验证了这两个变异分别遗传自患儿的父亲和母亲。此变异类型在gnomAD、ClinVar及HGMD等数据库均未见收录。结论PNP基因的c.150C>A变异与14q11.2拷贝数变异形成的复合杂合变异可能是该患儿的遗传学病因。这些发现为患儿父母提供了遗传咨询和产前诊断的依据,并进一步拓宽了PNP基因的变异谱。

Objective The objective of this study is to examine the clinical characteristics and genetic etiology of a pediatric patient presenting with purine nucleoside phosphorylase(PNP)deficiency.Methods In April 2021,a patient diagnosed with PNP deficiency was chosen as the subject of study at the Reproductive Genetics Clinic of Women's Hospital School of Medicine Zhejiang University.The children and their parents underwent family whole exome sequencing and subsequent bioinformatics analysis.The identified variants were subsequently confirmed through Sanger sequencing and SNP-Array techniques.Results The complex heterozygous variants,namely the PNP:c.150C>A variants and the 14q11.2 copy number variants,were detected.The confirmation of the inheritance of these two variants was achieved through the utilization of Sanger sequencing and SNP-Array analysis.The results of these analyses indicated that the PNP:c.150C>A variants were paternally inherited,whereas the 14q11.2 copy number variants were maternally inherited.Notably,these variant types were not found in the gnomAD,ClinVar,and HGMD databases.Conclusion The child's genetic etiology can be ascribed to the intricate heterozygous variation resulting from the c.150C>A variant of the PNP gene and the 14q11.2 copy number variation.These discoveries bear noteworthy implications for parental genetic counseling and prenatal diagnosis,while also augmenting the growing repertoire of observed variations in PNP genes.