A novel mutation in CLDN16 results in rare familial hypomagnesaemia with hypercalciuria and nephrocalcinosis in a Chinese family.

Background: Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessively inherited disease characterized by excessive wasting of renal tubular magnesium and calcium. FHHNC is associated with various mutations in CLDN16 and CLDN19.

Cases: Two children from a consanguineous family of Chinese Han origin demonstrated manifestations of rickets, polyuria, polydipsia, hematuria and failure to thrive. Hypomagnesaemia (0.49-0.50mmol/L), hypercalciuria or a trend to hypercalciuria (24hour urine calcium: 3.8-5.1mg/kg/day), and secondary hyperparathyroidism (serum PTH level: 94.7-200pg/mL) were revealed upon laboratory examination. Using targeted next-generation sequencing and subsequent confirmation by Sanger sequencing, a novel homozygous mutation was identified in the CLDN16 gene of both FHHNC patients. This specific mutation, a 16bp deletion followed by a 23bp insertion in exon 3, led to the generation of a premature termination codon. The parents and an unaffected sister were all heterozygous carriers of this mutation.

Conclusions: We detected a novel mutation in CLDN16 for the first time. The clinical and genetic findings from this study will help to expand the understanding of this rare disease, FHHNC.