Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD).

Autor: Islam S; Department Renal Medicine, University College London, London, UK., Tekman M; Department Renal Medicine, University College London, London, UK., Flanagan SE; Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK., Guay-Woodford L; Center for Translational Research, Children's National Hospital Health System, Washington, DC, USA., Hussain K; Department of Endocrinology, Sidra Medicine, Doha, Qatar., Ellard S; Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK., Kleta R; Department Renal Medicine, University College London, London, UK.; Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK., Bockenhauer D; Department Renal Medicine, University College London, London, UK.; Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK., Stanescu H; Department Renal Medicine, University College London, London, UK., Iancu D; Department Renal Medicine, University College London, London, UK.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2021 Dec; Vol. 9 (12), pp. e1674. Date of Electronic Publication: 2021 Apr 03.
DOI: 10.1002/mgg3.1674
Abstrakt: 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.
(© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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