Royal College of Surgeons in Ireland
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The genetic landscape of polycystic kidney disease in Ireland.

journal contribution
posted on 2021-01-21, 14:43 authored by Katherine Benson, Susan Murray, Sarah R.Senum, Elhussein Elhassan, Eoin T Conlon, Claire Kennedy, Shane Conlon, Edmund GilbertEdmund Gilbert, Dervla Connaughton, Paul O'Hara, Sarah Khamis, Sarah Cormican, Lawrence C. Brody, Anne M. Mollloy, Sally Ann Lynch, Liam Casserly, Matthew D. Griffin, Robert Carton, Kevin Yachnin, Peter C. Harris, Gianpiero CavalleriGianpiero Cavalleri, Peter Conlon
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.


Enterprise Partnership Scheme Fellowship Award (2019) from The Irish Research Council, in conjunction with Punchestown Kidney Research Fund (EPSPD/2019/213).

Beaumont Hospital Foundation

Irish Clinical Academic Training (ICAT) Programme

Royal Irish Academy

Royal College of Surgeons in Ireland

Wellcome Trust

Health Research Board (Grant Number 203930/B/16/Z)

Health Service Executive National Doctors Training and Planning

Health and Social Care, Research and Development Division, Northern Ireland



The original article is available at

Published Citation

Benson KA, Murray S, Senum SR, Elhassan E, Conlon ET, Kennedy C, Conlon S, Gilbert E, Connaughton D, O'Hara P, Khamis S, Cormican S, Brody LC, Molloy AM, Lynch SA, Casserly L, Griffin MD, Carton R, Yachnin K, Harris PC, Cavelleri GL, Conlon P. The genetic landscape of polycystic kidney disease in Ireland. European Journal of Human Genetics. 2021 [epub before print]

Publication Date

January 16 2021

PubMed ID



  • School of Pharmacy and Biomolecular Sciences
  • Beaumont Hospital




  • Accepted Version (Postprint)

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