Molecular pathology of X linked retinoschisis: mutations interfere with retinoschisin secretion and oligomerisation.

ABSTRACT:

Background/aim

X linked retinoschisis (XLRS) is caused by mutations in RS1 which encodes the discoidin domain protein retinoschisin, secreted by photoreceptors and bipolar cells. Missense mutations occur throughout the gene and some of these are known to interfere with protein secretion. This study was designed to investigate the functional consequences of missense mutations at different locations in retinoschisin.

Methods and results

The authors developed a structural model of the retinoschisin discoidin domain and used this to predict the effects of missense mutations. They expressed disease associated mutations and found that those affecting conserved residues prevented retinoschisin secretion. Most of the remaining mutations cluster within a series of loops on the surfac

SUBMITTER: Wang T 

PROVIDER: S-EPMC1856892 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature