HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, W. Articles by Seyama, Y. Search for Related Content PubMed PubMed Citation Articles by Chen, W. Articles by Seyama, Y. Social Bookmarking                      What's this?

The Journal of Lipid Research, Vol. 39, 509-517, March 1998
Copyright © 1998 by Lipid Research, Inc.

Original Article

Alternative pre-mRNA splicing of the sterol 27-hydroxylase gene (CYP 27) caused by a G to A mutation at the last nucleotide of exon 6 in a patient with cerebrotendinous xanthomatosis (CTX)

Correspondence to: Yousuke Seyama.

A recently identified G to A mutation at the last nucleotide of exon 6 of the sterol 27-hydroxylase gene (CYP 27) in a patient with cerebrotendinous xanthomatosis (CTX) was shown here to cause alternative pre-mRNA splicing of the gene. Northern blot analysis of the patient's RNA revealed a broadened band in the human CYP 27 mRNA region compared to that of the normal sample, indicating that there may exist differently spliced mRNA species in the patient. RT-PCR produced three fragments in the patient, one was full-length size and the other two were of smaller sizes. Sequence analysis confirmed that the nucleotide of the full-length size was identical to that of the normal full-length cDNA, except for the G to A mutation at codon 362, which corresponds to the last nucleotide of exon 6. One of the smaller size species lacked exon 6 and the other was absent from the 3' terminal 88 bp of exon 6 due to the use of an activated cryptic 5' splice site in exon 6. The correctly spliced mRNA harbouring the G to A mutation was responsible for the deficiency of the sterol 27-hydroxylase activity, as confirmed by transfection experiment. Transfection of constructed minigenes, with or without the mutation, showed that correctly spliced mRNA was observed in the normal minigene while the mutant minigene was differently spliced.

This is the first report of a G to A substitution at the last nucleotide of an exon resulting in both normal and abnormal pre-mRNA splicings, including exon skipping and activating of a coding region cryptic 5' splice site. The results reveal a new molecular basis for the CTX and provide information on aberrant splicing of pre-mRNA in multi-exon genes. —Chen, W., S. Kubota, and Y. Seyama. Alternative pre-mRNA splicing of the sterol 27-hydroxylase gene (CYP 27) caused by a G to A mutation at the last nucleotide of exon 6 in a patient with cerebrotendinous xanthomatosis (CTX). J. Lipid Res. 1998. 39: 509–517.

Supplementary key words: cerebrotendinous xanthomatosis, sterol 27-hydroxylase gene, mutation, alternative splicing

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K Ohno, A Tsujino, X-M Shen, M Milone, and A G Engel Spectrum of splicing errors caused by CHRNE mutations affecting introns and intron/exon boundaries J. Med. Genet., August 1, 2005; 42(8): e53 - e53. [Abstract] [Full Text] [PDF]

				P. D. James, L. A. O'Brien, C. A. Hegadorn, C. R. P. Notley, G. D. Sinclair, C. Hough, M.-C. Poon, and D. Lillicrap A novel type 2A von Willebrand factor mutation located at the last nucleotide of exon 26 (3538G>A) causes skipping of 2 nonadjacent exons Blood, November 1, 2004; 104(9): 2739 - 2745. [Abstract] [Full Text] [PDF]

				M.-H. Lee, S. Hazard, J. D. Carpten, S. Yi, J. Cohen, G. T. Gerhardt, G. Salen, and S. B. Patel Fine-mapping, mutation analyses, and structural mapping of cerebrotendinous xanthomatosis in U.S. pedigrees J. Lipid Res., February 1, 2001; 42(2): 159 - 169. [Abstract] [Full Text]

				A. Verrips, L. H. Hoefsloot, G. C. H. Steenbergen, J. P. Theelen, R. A. Wevers, F. J. M. Gabreels, B. G. M. van Engelen, and L. P. W. J. van den Heuvel Clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis Brain, May 1, 2000; 123(5): 908 - 919. [Abstract] [Full Text] [PDF]

				G. J. Schroepfer Jr. Oxysterols: Modulators of Cholesterol Metabolism and Other Processes Physiol Rev, January 1, 2000; 80(1): 361 - 554. [Abstract] [Full Text] [PDF]

				N. Wakamatsu, M. Hayashi, H. Kawai, H. Kondo, Y. Gotoda, Y. Nishida, R. Kondo, S. Tsuji, and T. Matsumoto Mutations producing premature termination of translation and an amino acid substitution in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis associated with parkinsonism J. Neurol. Neurosurg. Psychiatry, August 1, 1999; 67(2): 195 - 198. [Abstract] [Full Text] [PDF]