Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD).
Mol Genet Genomic Med
; 9(12): e1674, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-33811480
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regiões Promotoras Genéticas
/
Fosfotransferases (Fosfomutases)
/
Efeito Fundador
/
Hipoglicemia
/
Doenças Renais Policísticas
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Limite:
Female
/
Humans
/
Male
País/Região como assunto:
America do norte
/
Europa
Idioma:
En
Revista:
Mol Genet Genomic Med
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Reino Unido