Nature Genetics
1, 109 - 113 (1992)
doi:10.1038/ng0592-109
Aberrant splicing of the CHM gene is a significant cause of choroideremiaEeva-Marja Sankila, Ritva Tolvanen1, José A. J. M. van den Hurk2, Frans P. M. Cremers2
& Albert de la Chapelle1
1Department of Medical Genetics, University of Helsinki, Haartmaninkatu 3, SF-00290 Helsinki, Finland
2Department of Human Genetics, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands 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.
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