一例遗传性低磷血症性佝偻病伴高钙尿症患儿的临床特点及基因变异分析

Clinical feature and variant analysis of a case with hereditary hypophosphatemic rickets with hypercalciuria

目的探讨SLC34A3基因变异致遗传性低磷血症性佝偻病伴高钙尿症的临床特点及遗传学机制。方法总结1例不明原因的佝偻病伴低磷血症患儿的临床特点。提取患儿及父母外周血基因组DNA,应用高通量测序分析可能的致病变异基因,应用Sanger测序对患儿父母相关基因进行验证。结果患儿表现为身材矮小、佝偻病、低磷血症、高钙尿;基因测序结果显示患儿SLC34A3基因存在c.532_533delCA(p.Q178Vfs*6)及c.894_925+69del(splice)复合杂合变异,Sanger测序验证患儿父母都是这两个变异之一的无症状杂合变异携带者;根据美国医学遗传学与基因组学学会指南,2个变异均可评为致病性变异。结论SLC34A3基因c.532_533delCA(p.Q178Vfs*6)及c.894_925+69del(splice)复合杂合变异为该患儿的遗传学病因,两个变异既往均未见报道,丰富了人类遗传性低磷血症性佝偻病伴高钙尿症的基因变异谱,为家系的遗传咨询和产前诊断提供了依据。

Objective To explore the clinical features and genetic basis for a patient with hereditary hypophosphatemic rickets with hypercalciuria(HHRH).Methods Clinical data of the patient was collected.The patient was subjected to whole exome capture and next generation sequencing(NGS).Suspected variants were verified by Sanger sequencing.Results The patient presented with hypophosphatemic rickets,short stature,hypercalciuria,and renal stones.NGS showed that he has carried compound heterozygous variants of the SLC34A3 gene,namely c.532_533delCA(p.Q178Vfs*6)and c.894_925+69del(splicing).His parents were asymptomatic heterozygous carriers of one of the variants.Based on ACMG guidelines,both variants were classified as pathogenic.Conclusion The compound heterozygous variants c.532_533delCA(p.Q178Vfs*6)and c.894_925+69del(splicing)of the SLC34A3 gene probably underlie the disease in this child.Above finding has enriched the variant spectrum for HHRH.Based on the results,prenatal diagnosis may be provided for the family.