Genetic Complexity of Autosomal Dominant Polycystic Kidney and Liver Diseases.

Abstract

Data indicate significant phenotypic and genotypic overlap, plus a common pathogenesis, between two groups of inherited disorders, autosomal dominant polycystic kidney diseases (ADPKD), a significant cause of ESRD, and autosomal dominant polycystic liver diseases (ADPLD), which result in significant PLD with minimal PKD. Eight genes have been associated with ADPKD (PKD1 and PKD2), ADPLD (PRKCSH, SEC63, LRP5, ALG8, and SEC61B), or both (GANAB). Although genetics is only infrequently used for diagnosing these diseases and prognosing the associated outcomes, its value is beginning to be appreciated, and the genomics revolution promises more reliable and less expensive molecular diagnostic tools for these diseases. We therefore propose categorization of patients with a phenotypic and genotypic descriptor that will clarify etiology, provide prognostic information, and better describe atypical cases. In genetically defined cases, the designation would include the disease and gene names, with allelic (truncating/nontruncating) information included for PKD1 Recent data have shown that biallelic disease including at least one weak ADPKD allele is a significant cause of symptomatic, very early onset ADPKD. Including a genic (and allelic) descriptor with the disease name will provide outcome clues, guide treatment, and aid prevalence estimates.

• Authors: Emilie Cornec-Le Gall, Vicente E Torres, Peter C Harris
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 29 Issue 1 Pg. 13-23 (01 2018) ISSN: 1533-3450 [Electronic] United States
• PMID: 29038287 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2018 by the American Society of Nephrology.

Chemical References

• Calcium-Binding Proteins
• Intracellular Signaling Peptides and Proteins
• LRP5 protein, human
• Low Density Lipoprotein Receptor-Related Protein-5
• Membrane Proteins
• Molecular Chaperones
• RNA-Binding Proteins
• SEC Translocation Channels
• SEC61B protein, human
• SEC63 protein, human
• TRPP Cation Channels
• polycystic kidney disease 1 protein
• polycystic kidney disease 2 protein
• ALG8 protein, human
• Glucosyltransferases
• GANAB protein, human
• Glucosidases
• PRKCSH protein, human

Topics

• Alleles
• Calcium-Binding Proteins
• Cysts (diagnosis, epidemiology, genetics)
• Diagnosis, Differential
• Genetic Testing
• Glucosidases (genetics)
• Glucosyltransferases (genetics)
• Humans
• Intracellular Signaling Peptides and Proteins (genetics)
• Liver Diseases (diagnosis, epidemiology, genetics)
• Low Density Lipoprotein Receptor-Related Protein-5 (genetics)
• Membrane Proteins (genetics)
• Molecular Chaperones
• Molecular Diagnostic Techniques
• Mutation
• Phenotype
• Polycystic Kidney, Autosomal Dominant (diagnosis, epidemiology, genetics)
• Prognosis
• RNA-Binding Proteins
• SEC Translocation Channels (genetics)
• TRPP Cation Channels (genetics)