title: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC): report of three cases with a novel mutation in CLDN19 gene.
abstract: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder that is caused by mutation in the genes coding for tight junction proteins Claudin-16 and Claudin-19. Affected individuals usually develop nephrocalcinosis and progressive renal failure; some of them may have ophthalmologic involvement as well. Phenotypic description of three affected individuals from the same Middle Eastern kindred (two sisters and their cousin) is presented. This includes both clinical and laboratory findings upon initial presentation and subsequent follow-up. Molecular analysis of the CLDN19 gene was performed on the three cases and one set of parents. A novel homozygous missense mutation in CLDN19 (c.241C>T, p.Arg81Cys) was detected in all three affected children. The parents were heterozygous. Clinical and laboratory data in the three children with renal and ocular manifestations of FHHNC are described. Genetic analysis revealed a novel mutation in the CLDN19 gene. FHHNC is a rare cause of nephrocalcinosis, and we believe that it should be considered in the presence of nephrocalcinosis with hypercalcuria and hypermagnesuria.
authors.affiliation: Department of Pediatrics, Tawam Hospital, Al-Ain, United Arab Emirates. ashibli@tawamhospital.ae
authors.forename: Amar
authors.initials: A
authors.lastname: Al-Shibli
authors.forename: Martin
authors.initials: M
authors.lastname: Konrad
authors.forename: Waleed
authors.initials: W
authors.lastname: Altay
authors.forename: Omar
authors.initials: O
authors.lastname: Al Masri
authors.forename: Lihad
authors.initials: L
authors.lastname: Al-Gazali
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Al Attrach
mesh_terms: D002648:Child; D002675:Child, Preschool; D057167:Claudins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005128:Eye Diseases / Q000235:genetics / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008275:Magnesium Deficiency / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D020125:Mutation, Missense; D009397:Nephrocalcinosis / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D010375:Pedigree; D010641:Phenotype
chemical_list: C508912:CLDN19 protein, human; D057167:Claudins