The N-terminal p.(Ser38Cys) TIMP3 mutation underlying Sorsby fundus dystrophy is a founder mutation disrupting an intramolecular disulfide bond.

ABSTRACT: Sorsby fundus dystrophy (SFD) is a macular degeneration caused by mutations in TIMP3, the majority of which introduce a novel cysteine. However, the exact molecular mechanisms underlying SFD remain unknown. We aimed to provide novel insights into the functional consequences of a distinct N-terminal mutation. Haplotype reconstruction in three SFD families revealed that the identified c.113C>G, p.(Ser38Cys) mutation is a founder in Belgian and northern French families with a late-onset SFD phenotype. Functional consequences of the p.(Ser38Cys) mutation were investigated by high-resolution Western blot analysis of wild type and mutant TIMP3 using patient fibroblasts and in vitro generated proteins, and by molecular modeling of TIMP3 and its interaction partners. We could not confirm a previou

SUBMITTER: Naessens S 

PROVIDER: S-EPMC6594137 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature