Autosomal-Dominant Corneal Endothelial Dystrophies CHED1 and PPCD1 Are Allelic Disorders Caused by Non-coding Mutations in the Promoter of

Congenital hereditary endothelial dystrophy 1 (CHED1) and posterior polymorphous corneal dystrophy 1 (PPCD1) are autosomal-dominant corneal endothelial dystrophies that have been genetically mapped to overlapping loci on the short arm of chromosome 20. We combined genetic and genomic approaches to identify the cause of disease in extensive pedigrees comprising over 100 affected individuals. After exclusion of pathogenic coding, splice-site, and copy-number variations, a parallel approach using targeted and whole-genome sequencing facilitated the identification of pathogenic variants in a conserved region of the OVOL2 proximal promoter sequence in the index families (c.−339_361dup for CHED1 and c.−370T>C for PPCD1).

Source: The American Journal of Human Genetics - December 31, 2015 Category: Genetics & Stem Cells Authors: Alice E. Davidson, Petra Liskova, Cerys J. Evans, Lubica Dudakova, Lenka Nosková, Nikolas Pontikos, Hana Hartmannová, Kateřina Hodaňová, Viktor Stránecký, Zbyněk Kozmík, Hannah J. Levis, Nwamaka Idigo, Noriaki Sasai, Geoffrey J. Maher, James Tags: Article Source Type: research