Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive tubular disorder that is frequently associated with progressive renal failure. The primary defect is related to impaired tubular reabsorption of magnesium and calcium in the thick ascending limb of Henle's loop. Mutations in PCLN-1, which encodes the renal tight junction protein paracellin-1 (claudin-16), were identified as the underlying genetic defects. Comprehensive clinical data and the results of PCLN-1 mutation analysis of 25 FHHNC families with 33 affected individuals are presented. Patients presented mainly with urinary tract infections, polyuria, and hematuria at a median age of 3.5 yr. At the time of diagnosis, the GFR was already decreased to <60 ml/min per 1.73 m(2) for 11 patients. Twelve patients exhibited progression to end-stage renal disease, at a median age of 14.5 yr. Treatment with magnesium salts and thiazides seemed to have no effect on the progression of the disease. Genotype analysis revealed PCLN-1 mutations in all except three mutant alleles (94%). Fifteen different mutations were observed, including eight novel mutations. The accumulation of mutations affecting the first extracellular loop was striking, with 48% of all mutant alleles exhibiting a Leu151Phe exchange. Haplotype analysis strongly suggested a founder effect among patients with FHHNC who originated from Germany or eastern European countries. In 13 of 23 families, hypercalciuria and/or nephrolithiasis were observed in otherwise unaffected family members, indicating a possible role of heterozygous PCLN-1 mutations in yielding hypercalciuric stone-forming conditions.

• MeSH
• dítě MeSH
• fenotyp MeSH
• genotyp MeSH
• hořčík krev   MeSH
• klaudiny MeSH
• kohortové studie MeSH
• kojenec MeSH
• ledviny patofyziologie   MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• mladiství MeSH
• molekulární sekvence - údaje MeSH
• mutace genetika   MeSH
• nefrokalcinóza genetika   metabolismus   patofyziologie   MeSH
• předškolní dítě MeSH
• rodokmen MeSH
• sekvence aminokyselin genetika   MeSH
• vápník moč   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• claudin 16 MeSH Prohlížeč
• hořčík MeSH
• klaudiny MeSH
• membránové proteiny MeSH
• vápník MeSH