title: Mutation K42E in dehydrodolichol diphosphate synthase (DHDDS) causes recessive retinitis pigmentosa.
abstract: A single-nucleotide mutation in the gene that encodes DHDDS has been identified by whole exome sequencing as the cause of the non-syndromic recessive retinitis pigmentosa (RP) in a family of Ashkenazi Jewish origin in which three of the four siblings have early onset retinal degeneration. The peripheral retinal degeneration in the affected siblings was evident in the initial examination in 1992 and only one had detectable electroretinogram (ERG) that suggested cone-rod dysfunction. The pigmentary retinal degeneration subsequently progressed rapidly. The identified mutation changes the highly conserved residue Lys42 to Glu, resulting in lower catalytic efficiency. Patterns of plasma transferrin isoelectric focusing gel were normal in all family members, indicating no significant abnormality in protein glycosylation. Dolichols have been shown to influence the fluidity and of the membrane and promote vesicle fusion. Considering that photoreceptor outer segments contain stacks of membrane discs, we believe that the mutation may lead to low dolichol levels in photoreceptor outer segments, resulting in unstable membrane structure that leads to photoreceptor degeneration.
authors.affiliation: Bascom Palmer Eye Institute, University of Miami, 900 NW 17th St, 33136, Miami, FL, USA, BLam@med.miami.edu.
authors.forename: Byron L
authors.initials: BL
authors.lastname: Lam
authors.forename: Stephan L
authors.initials: SL
authors.lastname: Züchner
authors.forename: Julia
authors.initials: J
authors.lastname: Dallman
authors.forename: Rong
authors.initials: R
authors.lastname: Wen
authors.forename: Eduardo C
authors.initials: EC
authors.lastname: Alfonso
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Vance
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Peričak-Vance
mesh_terms: D000328:Adult; D019883:Alkyl and Aryl Transferases / Q000235:genetics* / Q000378:metabolism; D004286:Dolichols / Q000378:metabolism; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D012160:Retina / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D004286:Dolichols; D019883:Alkyl and Aryl Transferases; C051389:dehydrodolichyl diphosphate synthetase