Open AccessFounder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD)
Author(s) -
Islam Sumaya,
Tekman Mehmet,
Flanagan Sarah E.,
GuayWoodford Lisa,
Hussain Khalid,
Ellard Sian,
Kleta Robert,
Bockenhauer Detlef,
Stanescu Horia,
Iancu Daniela
Publication year - 2021
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1674
Subject(s) - haplotype , founder effect , genetics , biology , genotyping , single nucleotide polymorphism , mutation , population , 1000 genomes project , genotype , gene , medicine , environmental health
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.