| Title: | A founder UMOD variant is a common cause of hereditary nephropathy in the British population |
| Journal: | Journal of Medical Genetics |
| Published: | 29 Aug 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36038257/ |
| DOI: | https://doi.org/10.1136/jmg-2022-108704 |
| URL: | https://jmg.bmj.com/content/jmedgenet/early/2022/08/29/jmg-2022-108704.full.pdf |
| Citations: | 3 (3 in last 2 years) as of 8 Aug 2024 |
Publication 12257
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND: Monogenic disorders are estimated to account for 10%-12% of patients with kidney failure. We report the unexpected finding of an unusual uromodulin (UMOD) variant in multiple pedigrees within the British population and demonstrate a shared haplotype indicative of an ancestral variant.</p>
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 UMOD c.278_289delTCTGCCCCGAAG insCCGCCTCCT.</p>
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 UMOD variant by genome sequencing were detected in all of the 100K individuals, indicative of an extended shared haplotype.</p>
CONCLUSION: Our data confirm a likely founder UMOD variant with a wide geographical distribution within the UK. It should be suspected in cases of unexplained familial nephropathy presenting in patients of white British ancestry.</p>
66 Authors
- Manoj K Valluru
- Noelle KX Chung
- Mark Gilchrist
- Laura Butland
- Jackie Cook
- Anna Takou
- Abhijit Dixit
- Michael N Weedon
- Albert C M Ong
- John C Ambrose
- Prabhu Arumugam
- Roel Bevers
- Marta Bleda
- Freya Boardman-Pretty
- Christopher R Boustred
- Helen Brittain
- Mark J Caulfield
- Georgia C Chan
- Greg Elgar
- Tom Fowler
- Adam Giess
- Angela Hamblin
- Shirley Henderson
- Tim J P Hubbard
- Rob Jackson
- Louise J Jones
- Dalia Kasperaviciute
- Melis Kayikci
- Athanasios Kousathanas
- Lea Lahnstein
- Sarah E A Leigh
- Ivonne U S Leong
- Javier F Lopez
- Fiona MaleadyCrowe
- Meriel McEntagart
- Federico Minneci
- Loukas Moutsianas
- Michael Mueller
- Nirupa Murugaesu
- Anna C Need
- Peter O'Donovan
- Chris A Odhams
- Christine Patch
- Mariana Buongermino Pereira
- Daniel Perez-Gil
- John Pullinger
- Tahrima Rahim
- Augusto Rendon
- Tim Rogers
- Kevin Savage
- Kushmita Sawant
- Richard H Scott
- Afshan Siddiq
- Alexander Sieghart
- Samuel C Smith
- Alona Sosinsky
- Alexander Stuckey
- Mélanie Tanguy
- Ana Lisa TaylorTavares
- Ellen R A Thomas
- Simon R Thompson
- Arianna Tucci
- Matthew J Welland
- Eleanor Williams
- Katarzyna Witkowska
- Suzanne M Wood
Enabling scientific discoveries that improve human health