title: Localization of a gene for nonsyndromic renal hypodysplasia to chromosome 1p32-33.
abstract: Nonsyndromic defects in the urinary tract are the most common cause of end-stage renal failure in children and account for a significant proportion of adult nephropathy. The genetic basis of these disorders is not fully understood. We studied seven multiplex kindreds ascertained via an index case with a nonsyndromic solitary kidney or renal hypodysplasia. Systematic ultrasonographic screening revealed that many family members harbor malformations, such as solitary kidneys, hypodysplasia, or ureteric abnormalities (in a total of 29 affected individuals). A genomewide scan identified significant linkage to a 6.9-Mb segment on chromosome 1p32-33 under an autosomal dominant model with reduced penetrance (peak LOD score 3.5 at D1S2652 in the largest kindred). Altogether, three of the seven families showed positive LOD scores at this interval, demonstrating heterogeneity of the trait (peak HLOD 3.9, with 45% of families linked). The chromosome 1p32-33 interval contains 52 transcription units, and at least 23 of these are expressed at stage E12.5 in the murine ureteric bud and/or metanephric mesenchyme. These data show that autosomal dominant nonsyndromic renal hypodysplasia and associated urinary tract malformations are genetically heterogeneous and identify a locus for this common cause of human kidney failure.
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Sanna-Cherchi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Caridi
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Weng
authors.forename: Monica
authors.initials: M
authors.lastname: Dagnino
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
authors.forename: Anita
authors.initials: A
authors.lastname: Konka
authors.forename: Danio
authors.initials: D
authors.lastname: Somenzi
authors.forename: Alba
authors.initials: A
authors.lastname: Carrea
authors.forename: Claudia
authors.initials: C
authors.lastname: Izzi
authors.forename: Domenica
authors.initials: D
authors.lastname: Casu
authors.forename: Landino
authors.initials: L
authors.lastname: Allegri
authors.forename: Kai M
authors.initials: KM
authors.lastname: Schmidt-Ott
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barasch
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Ali G
authors.initials: AG
authors.lastname: Gharavi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000502:physiology*; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007668:Kidney / Q000002:abnormalities* / Q000473:pathology; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019683:Penetrance; D014515:Ureteral Diseases / Q000235:genetics*
chemical_list: D005819:Genetic Markers