title: Association of PKD2 (polycystin 2) mutations with left-right laterality defects.
abstract: Mutations in the PKD1 (polycystin 1) and PKD2 (polycystin 2) genes cause autosomal dominant polycystic kidney disease (ADPKD). Most Pkd2-null mouse embryos present with left-right laterality defects. For the first time, we report the association of ADPKD resulting from a mutation in PKD2 and left-right asymmetry defects. PKD1 and PKD2 were screened for mutations or large genomic rearrangements in 3 unrelated patients with ADPKD presenting with laterality defects: dextrocardia in one and situs inversus totalis in 2 others. A large gene deletion, a single-exon duplication, and an in-frame duplication respectively, were found in the 3 patients. These polymorphisms were found in all tested relatives with ADPKD, but were absent in unaffected related individuals. No left-right anomalies were found in other members of the 3 families. A possible association between heterotaxia and a PKD2 mutation in our 3 patients is suggested by: (1) the existence of laterality defects in Pkd2-null mouse and zebrafish models and (2) detection of a pathogenic PKD2 mutation in the 3 probands, although PKD2 mutations account for only 15% of ADPKD families. The presence of left-right laterality defects should be systematically screened in larger cohorts of patients with ADPKD harboring PKD2 mutations.
authors: Centre de Néphrologie et Transplantation Rénale, Hôpital La Conception, Marseille, France.
authors: Stanislas
authors: S
authors: Bataille
authors: Nathalie
authors: N
authors: Demoulin
authors: Olivier
authors: O
authors: Devuyst
authors: Marie-Pierre
authors: MP
authors: Audrézet
authors: Karin
authors: K
authors: Dahan
authors: Michel
authors: M
authors: Godin
authors: Michel
authors: M
authors: Fontès
authors: Yves
authors: Y
authors: Pirson
authors: Stéphane
authors: S
authors: Burtey
mesh_terms: D000368:Aged; D003914:Dextrocardia / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010009:Osteochondrodysplasias / Q000235:genetics*; D010179:Pancreas / Q000002:abnormalities; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000503:physiopathology*; D012857:Situs Inversus / Q000235:genetics*; D050396:TRPP Cation Channels / Q000235:genetics*
chemical_list: D050396:TRPP Cation Channels