Abdelhadi Ola, Iancu Daniela, Tekman Mehmet, Stanescu Horia, Bockenhauer Detlef, Kleta Robert
Centre for Nephrology University College London London UK.
Mol Genet Genomic Med. 2016 Jun 7;4(5):521-6. doi: 10.1002/mgg3.227. eCollection 2016 Sep.
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.
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.
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.
By knowing the prevalent mutation in a given population more efficient diagnostics can be performed and the families can benefit from specific counseling.
EAST综合征是一种由KCNJ10基因功能丧失性突变引起的常染色体隐性疾病。在目前已描述的14种致病突变中，p.R65P突变最为常见，且特别多见于巴基斯坦裔患者。因此，我们旨在确定巴基斯坦人群中是否存在潜在的奠基者效应。
为此，我们对来自7个家庭的12名患者进行了基因分型，并将疾病单倍型与种族匹配的对照染色体进行比较。该单倍型与巴基斯坦的人口统计数据一起用于估计这种奠基者突变的发生时间。
我们在KCNJ10基因p.R65P突变周围鉴定出一个小的纯合0.694 Mb区域，所有患者的该区域单倍型均相同，而对照样本中完全不存在。根据目前的人口统计数据和疾病频率知识，我们估计这种特定的p.R65P突变出现在20代（约500年）之前。
通过了解特定人群中流行的突变，可以进行更有效的诊断，家庭也可以从特定的咨询中受益。
