Author Affiliations: Department of Pediatrics, University of California, San Francisco, California 94143, USA (Seeley HH); Department of Pediatrics, University of California, Davis, California 95616, USA (Loomba-Albrecht LA, Butani L); Center for Nephrology and Metabolic Disorders, Laboratory for Molecular Diagnostics, Weisswasser, Germany (Nagel M); Department of Pediatrics, Vanderbilt University, Nashville, Tennessee 37232, USA (Bremer AA)

Corresponding Author: Andrew A. Bremer, MD, PhD, Division of Endocrinology, Vanderbilt University School of Medicine, 11136 Doctors' Office Tower, 2200 Children's Way, Nashville, TN 37232-9170, USA (Tel: 615-936-1874; Fax: 615-875-7633; Email: andrew.a.bremer@vanderbilt.edu)

doi: 10.1007/s12519-011-0295-3

Background: This article summarizes the varying clinical manifestations of three siblings with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) caused by the same genetic lesion.

Methods: The medical records of three siblings with FHHNC (one girl and two boys, aged 6 to 12 years) were reviewed and the clinical manifestations and treatment of their disease were described.

Results: Despite varying phenotypes, each sibling had the same genetic lesion—a novel homozygous mutation in CLDN16 (c.211A>G, M71V).

Conclusion: Although FHHNC is a rare disorder, this report is significant for the following reasons: (i) it describes a novel CLDN16 mutation causing FHHNC, adding to the literature of FHHNC-causing CLDN16 mutations; (ii) it suggests that genes other than CLDN16 or epigenetic factors are involved in the clinical spectrum of FHHNC; and (iii) it reinforces the variability of disease manifestation and genotype-phenotype correlations.

Key words: claudin-16; hypomagnesemia; hypercalciuria; nephrocalcinosis; paracellin-1