Autosomal dominant polycystic kidney disease: Localization of the second gene to chromosome 4q13–q23

• Published in: Genomics (San Diego, Calif.) Vol. 18; no. 3; pp. 467 - 472
• Main Authors: Kimberling, William J., Kumar, Shrawan, Gabow, Patricia A., Kenyon, Judith B., Connolly, Christopher J., Somlo, Stefan
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.12.1993; Elsevier
• Subjects: 550400 - Genetics; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; BODY; Chromosome Mapping; CHROMOSOMES; Chromosomes, Human, Pair 4; DISEASES; DNA - isolation & purification; Female; Genes, Dominant; Genetic Linkage; GENETIC MAPPING; HEREDITARY DISEASES; HUMAN CHROMOSOMES; Humans; KIDNEYS; Lymphocytes - metabolism; Male; MAPPING; Medical sciences; Nephrology. Urinary tract diseases; ORGANS; Polycystic Kidney, Autosomal Dominant - blood; Polycystic Kidney, Autosomal Dominant - genetics; Polymerase Chain Reaction; Urinary system involvement in other diseases. Miscellaneous; Genetic mapping; Human; Urinary system disease; Linkage; Genetic marker; Polycystic kidney; Renal disease; Genetic disease; B4-Chromosome; Heterogeneity; Gene; Microsatellite DNA; Cyst; Benign neoplasm; Polymorphism
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/S0888-7543(11)80001-7

At least two loci are known to exist for autosomal dominant polycystic kidney disease (ADPKD). One was localized to 16p, but the second less common locus has remained unlinked. Over 100 microsatellite markers, distributed across all chromosomes, have been typed on informative family members from the large Sicilian kindred in which the genetic heterogeneity was first discovered. Both the affected and the unaffected status of every family member used in the study were confirmed by renal ultrasonography. This search has resulted in the successful localization of a second ADPKD gene to chromosome 4q. It was found to be flanked by the markers D4S231 and D4S414, defining a segment that spans about 9 cM. The new locus has been designated PKD4. This second localization will allow researchers to target another ADPKD gene for isolation in an effort to understand the pathogenesis of this common disorder. Furthermore, when flanking markers for the second ADPKD gene are used in conjunction with flanking markers for PKD1, the accuracy of the diagnosis of the subtype of ADPKD present in any particular family will be enhanced. This will improve the accuracy of linkage-based presymptomatic diagnoses by reducing the error due to genetic heterogeneity.