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Objective. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare disease characterized by the renal loss of magnesium and calcium, and bilateral medullary nephrocalcinosis. It is caused by mutations in the CLDN16 and CLDN19 genes. In this study, we aimed to present the clinical and laboratory findings of five patients with two different pathogenic variations.
Methods. The clinical features and the detected variants in the CLDN16 gene of five children with FHHNC from two different families are presented.
Results. The median age of the five female patients included in the study was 11.2 years. The monoamniotic monochorionic twins from the first family had similar clinical and laboratory findings. In these patients, a previously defined pathogenic variant (a homozygous variant of c.710G>A (p.W237*)) in the CLDN16 gene was detected. The three sisters from the second family had variable eGFRs, height and weight SDS values, serum calcium, magnesium, uric acid, parathyroid hormone values, as well as variable 24-hour urine calcium, magnesium, citrate, protein, and fractional excretion of magnesium (FEMg 2+ %). A novel c.646C>A (p.R216S) homozygous, likely pathogenic variant was detected in the CLDN16 gene of the three sisters.
Conclusions. Our findings showed that, despite the same mutation, the clinical features of the siblings with FHHNC may differ significantly while monozygotic twins with the same mutation had similar phenotype. This suggests that some other genetic factors are playing a role in the renal failure process of patients with FHHNC who have mutations in the CLDN16 gene.
Cite this article as: Guler MA, Yüce Kahraman Ç. Evaluation of phenotypes and CLDN16 variants in 2 different familial hypomagnesemia with hypercalciuria and nephrocalcinosis families: Phenotypic differences in siblings and phenotypic similarity in monozygotic twins. Turk J Nephrol. 2023;32(1):63-72.