A founderUMODvariant is a common cause of hereditary nephropathy in the British population
| Autor: | Manoj K Valluru, Noelle KX Chung, Mark Gilchrist, Laura Butland, Jackie Cook, Anna Takou, Abhijit Dixit, Michael N Weedon, Albert C M Ong |
|---|---|
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Medical Genetics. 60:397-405 |
| ISSN: | 1468-6244 0022-2593 |
| DOI: | 10.1136/jmg-2022-108704 |
| Popis: | BackgroundMonogenic 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.MethodsProbands 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 ofUMODc.278_289delTCTGCCCCGAAG insCCGCCTCCT.ResultsA 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 UMODvariant by genome sequencing were detected in all of the 100K individuals, indicative of an extended shared haplotype.ConclusionOur data confirm a likely founderUMODvariant 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|