Phenotype and genotype heterogeneity in autosomal dominant polycystic kidney disease

• Published in: The Lancet (British edition) Vol. 340; no. 8831; pp. 1330 - 1333
• Main Authors: Ravine, D, Forrest, S.M, Sheffield, L.J, Danks, D.M, Walker, R.G, Kincaid-Smith, P, Gibson, R.N, Richards, R.I., Friend, K.
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 28.11.1992; Lancet; Elsevier Limited
• Subjects: Adolescent; Adult; Age Factors; Biological and medical sciences; Child; Child, Preschool; Chromosome 16; Chromosome Mapping - standards; Chromosomes; Cysts; Diagnosis, Differential; Disease; Evaluation Studies as Topic; Gene loci; Genetics; Genotype; Genotypes; Heterogeneity; Humans; Hypertension; Infant; Kidney diseases; Kidneys; Medical research; Medical sciences; Meiosis; Middle Aged; Mutation; Nephrology. Urinary tract diseases; Patients; Pedigree; Phenotype; Phenotypes; Polycystic kidney; Polycystic Kidney, Autosomal Dominant - diagnostic imaging; Polycystic Kidney, Autosomal Dominant - epidemiology; Polycystic Kidney, Autosomal Dominant - genetics; Polymorphism, Genetic; Prevalence; Recombination, Genetic; Renal failure; Renal function; Sensitivity and Specificity; Survival Rate; Ultrasonography; Urinary system involvement in other diseases. Miscellaneous; Victoria - epidemiology; Sonography; Human; Urinary system disease; Family study; Polycystic kidney; Mortality; Exploration; Renal disease; Genetic disease; Phenotype; Autosomal character; Genetics; Mutation; Comparative study
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/0140-6736(92)92503-8

It is now clear that mutations of at least two genetic loci can lead to autosomal dominant polycystic kidney disease (ADPKD). We have compared the clinical features of ADPKD caused by mutations at the PKD1 locus (linked to the α-globin complex on chromosome 16) with those of disease not linked to the locus (non-PKD1). We identified 18 families (285 affected members) with mutations at PKD1 and 5 families (49 affected individuals) in which involvement of this locus could be dismissed. Non-PKD1 patients lived longer than PKD1 patients (median survival 71·5 vs 56·0 years), had a lower risk of progressing to renal failure (odds ratio 0·35, 95% Cl 0·13-0·92), were less likely to have hypertension (odds ratio adjusted for age and family of origin 0·29, 0·11-0·80), were diagnosed at an older age (median 69·1 vs 44·8 years), and had fewer renal cysts at the time of diagnosis. Although most of the PKD1 families were ascertained through clinics treating patients with renal impairment, no non-PKD1 family was identified through this source. Non-PKD1 ADPKD has a much milder phenotype than that linked to PKD1. Partly as a result of this difference in severity, the reported prevalence of this genotype is probably an underestimate.