Abstract
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 (0.49-0.50 mmol/L), hypercalciuria or a trend to hypercalciuria (24 hour urine calcium: 3.8-5.1 mg/kg/day), and secondary hyperparathyroidism (serum PTH level: 94.7-200 pg/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 16 bp deletion followed by a 23 bp 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.
Original language | English |
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Pages (from-to) | 69-74 |
Number of pages | 6 |
Journal | Clinica Chimica Acta |
Volume | 457 |
DOIs | |
Publication status | Published - 1 Jun 2016 |
Externally published | Yes |
Keywords
- CLDN16
- Hypercalciuria
- Hypomagnesaemia
- Nephrocalcinosis
- Rickets