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.
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References
McKusick, V.A. Mendelian Inheritance in Man 9th edn (Johns Hopkins University Press, Baltimore, 1990).
McCulloch, C. & McCulloch, R.J.P. Trans. Am. Acad. Ophthalmol. Otolaryngol. 52, 160–190 (1948).
Sorsby Franceshetti, A., Joseph, R. & Davey, J.B. Br. J. Ophthalmol. 36, 547–581 (1952).
Kärnä, J. Acta Ophthalmol. (suppl) 176, 1–68 (1986).
Forsius, H., Eriksson, A.W. & Kärnä, J. in Population Structure and Genetic Disorders 605–609 (eds Eriksson, A.W., Forsius, H., Nevanlinna, H.R., Workman, P.L. & Norio, R.J. ) (Academic Press, London, 1980).
Sankila, E.-M. et al. Hum. Genet. 85, 117–120 (1990).
Cremers, F.P.M., van de Pol, T.J.R., van Kerkhoff, L.P.M., Wieringa, B. & Ropers, H.-H. Nature 347, 674–677 (1990).
Cremers, F.P.M. et al. Genomics 4, 41–46 (1989).
Cremers, F.P.M. et al. Am. J. hum. Genet. 47, 622–628 (1990).
Van den Hurk, J.A.J.M. et al. Am. J. hum. Genet. (In the press).
Sankila, E.-M. et al. Clin. Genet. 31, 315–322 (1987).
Sankila, E.-M. et al. Hum. Genet. 84, 66–70 (1989).
Sankila, E.-M., Sistonen, P., Cremers, F.P.M. & de la Chapelle, A. Hum. Genet. 87, 348–352 (1991).
Orita, M., Suzuki, Y., Sekiya, T. & Hayashi, K. Genomics 5, 874–879 (1989).
Saiki, R.K. et al. Science 230, 1350–1354 (1985).
Schneider-Gädicke, A., Beer-Romero, P., Brown, L.G., Nussbaum, R. & Page, D.C. Cell 57, 1247–1258 (1989).
Roberts, R.G., Barby, T.F.M., Manners, E., Bobrow, M. & Bentley, D.R. Am. J. hum. Genet. 49, 298–310 (1991).
Srivastava, A.K., Montanaro, V. & Kere, J. PCR Methods and Applications (in the press).
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Sankila, EM., Tolvanen, R., van den Hurk, J. et al. Aberrant splicing of the CHM gene is a significant cause of choroideremia. Nat Genet 1, 109–113 (1992). https://doi.org/10.1038/ng0592-109
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DOI: https://doi.org/10.1038/ng0592-109
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