The genetic landscape of polycystic kidney disease in Ireland.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
01
07
2020
accepted:
21
12
2020
revised:
16
12
2020
pubmed:
18
1
2021
medline:
18
1
2022
entrez:
17
1
2021
Statut:
ppublish
Résumé
Polycystic kidney diseases (PKDs) comprise the most common Mendelian forms of renal disease. It is characterised by the development of fluid-filled renal cysts, causing progressive loss of kidney function, culminating in the need for renal replacement therapy or kidney transplant. Ireland represents a valuable region for the genetic study of PKD, as family sizes are traditionally large and the population relatively homogenous. Studying a cohort of 169 patients, we describe the genetic landscape of PKD in Ireland for the first time, compare the clinical features of patients with and without a molecular diagnosis and correlate disease severity with autosomal dominant pathogenic variant type. Using a combination of molecular genetic tools, including targeted next-generation sequencing, we report diagnostic rates of 71-83% in Irish PKD patients, depending on which variant classification guidelines are used (ACMG or Mayo clinic respectively). We have catalogued a spectrum of Irish autosomal dominant PKD pathogenic variants including 36 novel variants. We illustrate how apparently unrelated individuals carrying the same autosomal dominant pathogenic variant are highly likely to have inherited that variant from a common ancestor. We highlight issues surrounding the implementation of the ACMG guidelines for variant pathogenicity interpretation in PKD, which have important implications for clinical genetics.
Identifiants
pubmed: 33454723
doi: 10.1038/s41431-020-00806-5
pii: 10.1038/s41431-020-00806-5
pmc: PMC8110806
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
827-838Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK058816
Pays : United States
Organisme : Wellcome Trust
ID : 203930/B/16/Z
Pays : United Kingdom
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