title: Refined mapping of a gene (NPH1) causing familial juvenile nephronophthisis and evidence for genetic heterogeneity.
abstract: Familial juvenile nephronophthisis (NPH) is an autosomal recessive progressive tubulo-interstitial kidney disorder, responsible for 6-10% of end-stage renal failure in children, and is frequently associated with Leber amaurosis (termed Senior-Løken syndrome). The biochemical basis of NPH is unknown. We recently reported linkage of the purely renal form of NPH to three markers on chromosome 2. Our results also suggested the existence of genetic heterogeneity between NPH and SLS. To map this NPH gene more precisely, we have now tested the segregation of six new microsatellite markers and five additional families. Haplotype analyses show unequivocally that four NPH families are not linked to the chromosome 2 markers, although there are no clinical or pathological features discernible in these families that could separate them from the families linked to the chromosome 2 NPH locus (NPH1). This reveals genetic heterogeneity in the purely renal form of NPH. In situ hybridization of YAC clones isolated with two closely linked markers assigned the NPH1 region to 2q13. Furthermore, based on haplotype analysis and specific recombination events, the NPH1 gene has been placed between D2S293/D2S340 and D2S121, a genetic interval of about 5-7 cM.
authors: INSERM U192, Hôpital Necker-Enfants Malades, Paris, France.
authors: M
authors: M
authors: Medhioub
authors: D
authors: D
authors: Cherif
authors: F
authors: F
authors: Benessy
authors: F
authors: F
authors: Silbermann
authors: M C
authors: MC
authors: Gubler
authors: D
authors: D
authors: Le Paslier
authors: D
authors: D
authors: Cohen
authors: J
authors: J
authors: Weissenbach
authors: J
authors: J
authors: Beckmann
authors: C
authors: C
authors: Antignac
mesh_terms: D002889:Chromosomes, Human, Pair 2; D004276:DNA, Satellite / Q000235:genetics; D005260:Female; D005796:Genes; D005808:Genes, Recessive; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D017044:Polycystic Kidney, Autosomal Recessive / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D004276:DNA, Satellite; D005819:Genetic Markers