Phenotypic Discordance among Siblings with Autosomal Recessive Polycystic Kidney Disease: Case Report and Review of the Literature.

Autor:	Henein M; Division of Medical Genetics, McGill University Health Centre, Montreal, Québec, Canada, marc.henein@mail.mcgill.ca., Russo F; Division of Medical Genetics, McGill University Health Centre, Montreal, Québec, Canada., Sentell ZT; Department of Human Genetics, McGill University, Montreal, Québec, Canada.; Research Institute of the McGill University Health Centre, Montreal, Québec, Canada., Goupil R; Department of Nephrology, Hôpital du Sacré-Cœur de Montréal, Montreal, Québec, Canada., Kitzler TM; Division of Medical Genetics, McGill University Health Centre, Montreal, Québec, Canada.; Department of Human Genetics, McGill University, Montreal, Québec, Canada.; Research Institute of the McGill University Health Centre, Montreal, Québec, Canada.
Jazyk:	angličtina
Zdroj:	Nephron [Nephron] 2024 Aug 05, pp. 1-9. Date of Electronic Publication: 2024 Aug 05.
DOI:	10.1159/000540741
Abstrakt:	Missense variants in the PKHD1 gene are associated with the full spectrum of autosomal recessive polycystic kidney disease severity and exhibit variable expressivity. The study of clinical expressivity is limited by the extensive allelic heterogeneity within the PKHD1 gene, which encodes a 4074-amino-acid protein. We report the case of adult siblings with biallelic missense PKHD1 variants, c.4870C>T (p.Arg1624Trp) and c.8206T>G (p.Trp2736Gly), who presented with discordant phenotypes. Patient A developed progressive chronic kidney disease and Caroli syndrome in childhood requiring combined liver and kidney transplantation, while patient B remains minimally affected in the fourth decade of life with normal kidney function and signs of medullary sponge kidney on imaging. We review previously reported cases of phenotypic discordance among siblings and suggest that genotypes composed of at least one hypomorphic missense variant are more likely to lead to phenotypic discordance. (© 2024 The Author(s). Published by S. Karger AG, Basel.)
Databáze:	MEDLINE
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