Abstract:

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.

Key words: CLDN16 gene, Familial hypomagnesemia with hypercalciuria and nephrocalcinosis, Ricket, Hypomagnesemia, Hypercalciuria, Nephrocalcinosis