Islam, S;
Tekman, M;
Flanagan, SE;
Guay-Woodford, L;
Hussain, K;
Ellard, S;
Kleta, R;
... Iancu, D; + view all
(2021)
Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD).
Molecular Genetics & Genomic Medicine
, Article e1674. 10.1002/mgg3.1674.
(In press).
Preview |
Text
mgg3.1674.pdf - Published Version Download (1MB) | Preview |
Abstract
BACKGROUND: Polycystic kidney disease with hyperinsulinaemic hypoglycaemia (HIPKD) is a recently described disease caused by a single nucleotide variant, c.-167G>T, in the promoter region of PMM2 (encoding phosphomannomutase 2), either in homozygosity or compound heterozygosity with a pathogenic coding variant in trans. All patients identified so far are of European descent, suggesting a possible founder effect. METHODS: We generated high density genotyping data from 11 patients from seven unrelated families, and used this information to identify a common haplotype that included the promoter variant. We estimated the age of the promoter mutation with DMLE+ software, using demographic parameters corresponding to the European population. RESULTS: All patients shared a 0.312 Mb haplotype which was absent in 503 European controls available in the 1000 Genomes Project. The age of this mutation was estimated as 105-110 generations, indicating its occurrence around 600 BC, a time of intense migration, which might explain the presence of the same mutations in Europeans around the globe. CONCLUSION: The shared unique haplotype among seemingly unrelated patients is consistent with a founder effect in Europeans.
| Type: | Article |
|---|---|
| Title: | Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD) |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/mgg3.1674 |
| Publisher version: | https://doi.org/10.1002/mgg3.1674 |
| Language: | English |
| Additional information: | Copyright © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | PMM2 gene, founder effect, hyperinsulinism, hypoglycaemia, polycystic kidney disease, promoter |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10126103 |
Archive Staff Only
 |
View Item |
