title: Aberrant splicing of the CHM gene is a significant cause of choroideremia.
abstract: Choroideremia (CHM) is an X-linked progressive degeneration of the choroid and retina. 12% of unrelated male patients carry deletions of the partially cloned CHM gene. In Finland, there are more than 120 living CHM patients belonging to eight apparently unrelated pedigrees. Molecular deletions involving the CHM gene have been detected in three families. We have screened the remaining five families for point mutations. In one large family a single nucleotide (T) insertion into the donor splice site of exon C leads to two aberrantly spliced mRNAs both producing a premature stop codon. The mutation can be assayed easily by amplification and digestion with Msel. Our findings provide additional evidence for the pathogenetic role of CHM mutations and provide a diagnostic tool for one fifth of the world's known CHM patients.
authors.affiliation: Department of Medical Genetics, University of Helsinki, Finland.
authors.forename: E M
authors.initials: EM
authors.lastname: Sankila
authors.forename: R
authors.initials: R
authors.lastname: Tolvanen
authors.forename: J A
authors.initials: JA
authors.lastname: van den Hurk
authors.forename: F P
authors.initials: FP
authors.lastname: Cremers
authors.forename: A
authors.initials: A
authors.lastname: de la Chapelle
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015794:Choroideremia / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005387:Finland; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing / Q000235:genetics*
chemical_list: D004247:DNA