title: Haplotype analysis of CLDN19 single nucleotide polymorphisms in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
abstract: 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.
authors.affiliation: Unidad de Investigacion, Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Martin-Nuñez
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cordoba-Lanus
authors.forename: Hilaria
authors.initials: H
authors.lastname: Gonzalez-Acosta
authors.forename: Aniana
authors.initials: A
authors.lastname: Oliet
authors.forename: Elvira
authors.initials: E
authors.lastname: Izquierdo
authors.forename: Felix
authors.initials: F
authors.lastname: Claverie-Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D057167:Claudins / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006239:Haplotypes; D006801:Humans; D053565:Hypercalciuria / Q000150:complications / Q000235:genetics*; D015994:Incidence; D008275:Magnesium Deficiency / Q000150:complications / Q000235:genetics*; D008297:Male; D009397:Nephrocalcinosis / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D013030:Spain / Q000453:epidemiology; D055815:Young Adult
chemical_list: C508912:CLDN19 protein, human; D057167:Claudins