A novel homozygous nonsense mutation in CABP4 causes congenital cone-rod synaptic disorder. Invest

PURPOSE. The purpose of this study was to identify the caus-ative gene defect in two siblings with an uncharacterized cone–rod dysfunction and to describe the clinical characteris-tics. METHODS. Genome-wide homozygosity mapping, with a 250K SNP-array followed by a search for candidate genes, was per-formed. The patients underwent ophthalmic examination, in-cluding elaborate electroretinography. RESULTS. In a Dutch sib pair, a shared 9-Mb homozygous region was found on 11q13.1-q13.5 that encompasses the CABP4 gene, previously implicated in autosomal recessive incomplete congenital stationary night blindness (CSNB2) in two small families. A novel homozygous p.Arg216X mutation in CABP4 was detected in the sib pair. Quantitative RT-PCR on RNA isolated from patient lymphoblast cells showed no nonsense