Altered rep-1 expression due to substitution at position +3 of the IVS13 splice-donor site of the choroideremia (CHM) gene.
OBJECTIVE
To characterize the effect on mRNA splicing of a yet undescribed mutation located in intron 13 splice-donor sequence (IVS13 + 3A --> C) in the Rab-Escort-protein 1 gene of a patient with choroideremia.


METHODS
The base substitution was firstly detected by the Single Strand conformation analysis from genomic DNA. A REP-1 cDNA region encompassing exons 10-14 was then specifically amplified from lymphocytes-derived mRNA.


RESULTS
We could demonstrate that this substitution affects REP-1 RNA processing. The patient revealed only one aberrantly spliced mRNA lacking exon 13 and no normal transcript.


CONCLUSIONS
The skipping of exon 13 results in the creation of a stop codon at the misspliced junction. This is the first case of nucleotide substitution at the +3 position of a splice donor site so far described in choroideremia.
Laboratoire de Biochimie Génétique, CNRS ERS 155, Institut de Biologie, Montpellier, France.
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L
Beaufrère
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Rieu
J C
JC
Hache
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Dumur
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Claustres
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Tuffery
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D019883:Alkyl and Aryl Transferases; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D015794:Choroideremia / Q000235:genetics* / Q000473:pathology; D016384:Consensus Sequence; D004274:DNA, Recombinant; D005091:Exons / Q000235:genetics; D005451:Fluorescein Angiography; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D020691:rab GTP-Binding Proteins
D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human; D002352:Carrier Proteins; D004274:DNA, Recombinant; D012333:RNA, Messenger; D019883:Alkyl and Aryl Transferases; D020691:rab GTP-Binding Proteins