CLDN16基因突变致家族性低镁血症高钙尿症伴肾钙质沉着症基因型与表型特点分析

Genotype and phenotype analysis of familial hypomagnesemia with hypercalciuria and nephrocalcinosis caused by CLDN16 mutation

目的探讨以严重佝偻病为主要表现的CLDN16基因突变致家族性低镁血症高钙尿症伴肾钙质沉着症(FHHNC)的基因型与临床表型特点。方法回顾性分析1例以严重佝偻病为主要表现的FHHNC患儿的临床资料及相关检查结果,并进行家系调查及基因测序。结果体格检查示患儿发育落后,特殊面容(鼻梁塌平、眼距宽、颈短),鸡胸,四肢弯曲畸形,肘关节及膝关节膨大,被动盘腿坐位。实验室检测结果示血钙、血镁降低,尿钙升高,25-羟基维生素D降低。影像学检查结果示骨骼系统异常。全外显子基因测序提示患儿CLDN16基因存在“错义变异C.647G>A,p.Arg216His(纯合子)”,患儿父母携带该位点变异(杂合子)。结合相关检查结果明确诊断为FHHNC。结论FHHNC由CLDN16/CLDN19基因突变引起,以低镁血症、高钙尿症、肾钙质沉着症以及进行性慢性肾功能衰竭为特征,可伴佝偻病等骨骼系统异常。全外显子基因测序可辅助诊断FHHNC。

Objective To investigate the genotype and phenotype characteristics of familial hypomagnesemia with hypercalciuria and nephrocalcinosis(FHHNC)caused by CLDN16 mutation.Methods The clinical data and laboratory determination results of a case of FHHNC were analyzed retrospectively,and pedigree survey and gene sequencing were performed.Results Physical examination showed backward development,special features(flat nose,wide eye space,short neck),chicken breast,bent limbs,enlarged elbow and knee joints and passive cross-legged sitting.Laboratory determination results showed decreased blood calcium and magnesium,increased urinary calcium and decreased 25-hydroxyvitamin D.Imaging revealed skeletal system abnormalities.Whole exon gene sequencing indicated that the CLDN16 gene of the case had"missense variation c.647G>A,p.arg216his(homozygous)",and the parents of the case carried this locus variation(heterozygous).Combined with the results of relevant tests,the diagnosis was FHHNC clearly.Conclusions FHHNC is involved in CLDN16/CLDN19 gene mutations.FHHNC patients usually exhibit hypomagnesemia with hypercalciuria and nephrocalcinosis,and it can accompanied by ricket and other skeletal system abnormalities.Whole exon sequencing can be helpful for FHHNC diagnosis.