Background: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive tubular disease caused by mutations in the CLDN16 or CLDN19 gene. Previous studies using microsatellite markers flanking the CLDN19 locus estimated that p.G20D (c.59G>A), a recurrent mutation in Spanish families, is a founder mutation. In the present study, we assessed the haplotype of Spanish patients using single nucleotide polymorphisms (SNPs).
Methods: Twenty-seven FHHNC patients were included in this study. We analyzed four SNPs located in CLDN19 introns 3 and 4 by polymerase chain reaction amplification and DNA sequencing.
Results: Three new patients with homozygous p.G20D were identified. The SNP genotyping analysis showed that alleles carrying this mutation shared a common SNP haplotype.
Conclusions: Our findings suggest the existence of a founder effect responsible for FHHNC in our cohort. Testing for the presence of mutation p.G20D should be the first genetic screening in Spanish patients.