A novel CLDN16 mutation in familial hypomagnesemia with hypercalciuria and nephrocalcinosis


Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubulopathy caused by mutations in either the CLDN16 or CLDN19 genes. Two children from a consanguineous family of Chinese presented with enuresis, polyuria, polydipsia, and failure to thrive. Laboratory studies revealed hypomagnesemia, hypercalciuria, sterile leukocyturia, microscopic hematuria, and renal insufficiency. Renal ultrasound showed bilateral medullary nephrocalcinosis and urolithiasis. Gene sequencing showed compound heterozygous, missense mutations c.416C>T (p.Ala139Val) and c.320T>C (p.Leu107Pro) within CLDN16 gene in both patients, and the mutation c.320T>C (p.Leu107Pro) had never been described before. The genetic findings will expand the understanding of FHHNC.