title: Identification of a novel oligomerization disrupting mutation in CRYΑA associated with congenital cataract in a South Australian family.
abstract: Congenital cataract is a heterogeneous disorder causing severe visual impairment in affected children. We screened four South Australian families with autosomal dominant congenital cataract for mutations in 10 crystallin genes known to cause congenital cataract. We identified a novel segregating heterozygous mutation, c.62G>A (p.R21Q), in the CRYΑA gene in one family. Western blotting of proteins freshly extracted from cataractous lens material of the proband demonstrated a marked reduction in the amount of the high-molecular-weight oligomers seen in the lens material of an unaffected individual. We conclude that the p.R21Q mutation, which is located in the highly conserved and structurally significant N-terminal region of the protein, is responsible for the cataract phenotype observed in the family as this mutation likely reduces the formation of the functional oligomeric alpha-crystallin.
authors.affiliation: Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, SA, Australia.
authors.forename: Kate J
authors.initials: KJ
authors.lastname: Laurie
authors.forename: Alpana
authors.initials: A
authors.lastname: Dave
authors.forename: Tania
authors.initials: T
authors.lastname: Straga
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Souzeau
authors.forename: Timothy
authors.initials: T
authors.lastname: Chataway
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sykes
authors.forename: Theresa
authors.initials: T
authors.lastname: Casey
authors.forename: Theodosia
authors.initials: T
authors.lastname: Teo
authors.forename: John
authors.initials: J
authors.lastname: Pater
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
authors.forename: Shiwani
authors.initials: S
authors.lastname: Sharma
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
mesh_terms: D015153:Blotting, Western; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D003459:Crystallins / Q000235:genetics*; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D013021:South Australia; D038201:alpha-Crystallins / Q000235:genetics*
chemical_list: C511246:CRYAA protein, human; D003459:Crystallins; D038201:alpha-Crystallins