title: Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome.
abstract: BACKGROUND
  EAST syndrome is an autosomal recessive disorder caused by loss-of-function mutations in the gene KCNJ10. Among the 14 pathogenic mutations described so far, the p.R65P mutation stands out as the most frequent one and is particularly associated with patients of Pakistani origin. As a result we aimed to establish the existence of a potential founder effect in the Pakistani population.
  
  
  METHODS
  To this end, we genotyped 12 patients from seven families and we compared disease haplotypes with ethnically matched control chromosomes. This haplotype was used together with demographic data for Pakistan to estimate the age of this founder mutation.
  
  
  RESULTS
  We identified a small homozygous 0.694 Mb region around the KCNJ10 p.R65P mutation that had identical haplotypes in all of the patients which were completely absent in the control sample. Based on current demographic data and knowledge about disease frequency, we estimate that this particular p.R65P mutation arose 20 generations (about 500 years) ago.
  
  
  CONCLUSIONS
  By knowing the prevalent mutation in a given population more efficient diagnostics can be performed and the families can benefit from specific counseling.
authors.affiliation: Centre for Nephrology University College London London UK.
authors.forename: Ola
authors.initials: O
authors.lastname: Abdelhadi
authors.affiliation: Centre for Nephrology University College London London UK.
authors.forename: Daniela
authors.initials: D
authors.lastname: Iancu
authors.affiliation: Centre for Nephrology University College London London UK.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tekman
authors.affiliation: Centre for Nephrology University College London London UK.
authors.forename: Horia
authors.initials: H
authors.lastname: Stanescu
authors.affiliation: Centre for Nephrology University College London London UK.
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
authors.affiliation: Centre for Nephrology University College London London UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Kleta
keywords: Ataxia; Kir4.1; epilepsy; kidney; potassium channel; tubulopathy