A founder
diagnosis
founder effect
genetic counseling
genetics, population
mutation
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
13
05
2022
accepted:
10
08
2022
pubmed:
30
8
2022
medline:
23
3
2023
entrez:
29
8
2022
Statut:
ppublish
Résumé
Monogenic disorders are estimated to account for 10%-12% of patients with kidney failure. We report the unexpected finding of an unusual uromodulin Probands from 12 apparently unrelated pedigrees with a family history of kidney failure within a geographically contiguous UK region were shown to be heterozygous for a pathogenic variant of A total of 88 clinically affected individuals were identified, all born in the UK and of white British ethnicity. 20 other individuals with the variant were identified in the UK 100,000 Genomes (100K) Project and 9 from UK Biobank (UKBB). A common extended haplotype was present in 5 of the UKBB individuals who underwent genome sequencing which was only present in <1 in 5000 of UKBB controls. Significantly, rare variants (<1 in 250 general population) identified within 1 Mb of the Our data confirm a likely founder
Sections du résumé
BACKGROUND
Monogenic disorders are estimated to account for 10%-12% of patients with kidney failure. We report the unexpected finding of an unusual uromodulin
METHODS
Probands from 12 apparently unrelated pedigrees with a family history of kidney failure within a geographically contiguous UK region were shown to be heterozygous for a pathogenic variant of
RESULTS
A total of 88 clinically affected individuals were identified, all born in the UK and of white British ethnicity. 20 other individuals with the variant were identified in the UK 100,000 Genomes (100K) Project and 9 from UK Biobank (UKBB). A common extended haplotype was present in 5 of the UKBB individuals who underwent genome sequencing which was only present in <1 in 5000 of UKBB controls. Significantly, rare variants (<1 in 250 general population) identified within 1 Mb of the
CONCLUSION
Our data confirm a likely founder
Identifiants
pubmed: 36038257
pii: jmg-2022-108704
doi: 10.1136/jmg-2022-108704
pmc: PMC10086494
doi:
Substances chimiques
Uromodulin
0
UMOD protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
397-405Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T00200X/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : British Heart Foundation
Pays : United Kingdom
Investigateurs
John C Ambrose
(JC)
Prabhu Arumugam
(P)
Roel Bevers
(R)
Marta Bleda
(M)
Freya Boardman-Pretty
(F)
Christopher R Boustred
(CR)
Helen Brittain
(H)
Mark J Caulfield
(MJ)
Georgia C Chan
(GC)
Greg Elgar
(G)
Tom Fowler
(T)
Adam Giess
(A)
Angela Hamblin
(A)
Shirley Henderson
(S)
Tim J P Hubbard
(TJP)
Rob Jackson
(R)
Louise J Jones
(LJ)
Dalia Kasperaviciute
(D)
Melis Kayikci
(M)
Athanasios Kousathanas
(A)
Lea Lahnstein
(L)
Sarah E A Leigh
(SEA)
Ivonne U S Leong
(IUS)
Javier F Lopez
(JF)
Fiona MaleadyCrowe
(F)
Meriel McEntagart
(M)
Federico Minneci
(F)
Loukas Moutsianas
(L)
Michael Mueller
(M)
Nirupa Murugaesu
(N)
Anna C Need
(AC)
Peter O'Donovan
(P)
Chris A Odhams
(CA)
Christine Patch
(C)
Mariana Buongermino Pereira
(MB)
Daniel Perez-Gil
(D)
John Pullinger
(J)
Tahrima Rahim
(T)
Augusto Rendon
(A)
Tim Rogers
(T)
Kevin Savage
(K)
Kushmita Sawant
(K)
Richard H Scott
(RH)
Afshan Siddiq
(A)
Alexander Sieghart
(A)
Samuel C Smith
(SC)
Alona Sosinsky
(A)
Alexander Stuckey
(A)
Mélanie Tanguy
(M)
Ana Lisa TaylorTavares
(AL)
Ellen R A Thomas
(ERA)
Simon R Thompson
(SR)
Arianna Tucci
(A)
Matthew J Welland
(MJ)
Eleanor Williams
(E)
Katarzyna Witkowska
(K)
Suzanne M Wood
(SM)
Informations de copyright
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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