This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted 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 Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yamaguchi, H. Articles by Matsukura, S. Search for Related Content PubMed PubMed Citation Articles by Yamaguchi, H. Articles by Matsukura, S.

A 5'-Splice Site Mutation in the Cytochrome P450 Steroid 17-Hydroxylase Gene in 17-Hydroxylase Deficiency

Third Department of Internal Medicine, Miyazaki Medical College (H.Y., M.N., M.M., S.M.), Kiyotake, Miyazaki 889–16; and the National Cardiovascular Center Research Institute (M.M., K.K.), Suita, Osaka 565, Japan

Address all correspondence and requests for reprints to: Masamitsu Nakazato, M.D., Ph.D., Third Department of Internal Medicine, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889–16, Japan. E-mail: nakazato{at}post.miyazaki-med.ac.jp

17-Hydroxylase deficiency (17OHD) is an autosomal recessive disorder that produces an excess of mineralocorticoids and sexual differentiation abnormalities. Using DNA sequencing analysis of the 17-hydroxylase (CYP17) gene from a Japanese patient with 17OHD, we identified a new type of genetic abnormality in this disease, a G to A transition at position +5 in the splice donor site of intron 7 of the CYP17 gene. In vitro expression analysis of an allelic minigene that consists of exons 6–8 of the patient’s CYP17 gene showed that the transition causes the skipping of exon 7. This exon skipping alters the translational reading frame of exon 8 and introduces a premature stop codon (TAA) at amino acid position 410 proximal to the heme iron-binding site essential for the enzymatic activity of CYP17. Restriction enzyme analysis showed that the patient is homozygous for the mutated CYP17 gene, and the parents are heterozygotes. This is the first reported patient with 17OHD caused by the splice site mutation in the CYP17 gene.

This article has been cited by other articles:

				T. Kubo, S.-R. Kim, K. Sai, Y. Saito, T. Nakajima, K. Matsumoto, H. Saito, K. Shirao, N. Yamamoto, H. Minami, et al. FUNCTIONAL CHARACTERIZATION OF THREE NATURALLY OCCURRING SINGLE NUCLEOTIDE POLYMORPHISMS IN THE CES2 GENE ENCODING CARBOXYLESTERASE 2 (HCE-2) Drug Metab. Dispos., October 1, 2005; 33(10): 1482 - 1487. [Abstract] [Full Text] [PDF]

				M. Costa-Santos, C. E. Kater, E. P. Dias, and R. J. Auchus Two Intronic Mutations Cause 17-Hydroxylase Deficiency by Disrupting Splice Acceptor Sites: Direct Demonstration of Aberrant Splicing and Absent Enzyme Activity by Expression of the Entire CYP17 Gene in HEK-293 Cells J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 43 - 48. [Abstract] [Full Text] [PDF]

				R. M. Martin, C. J. Lin, E. M. F. Costa, M. L. de Oliveira, A. Carrilho, H. Villar, C. A. Longui, and B. B. Mendonca P450c17 Deficiency in Brazilian Patients: Biochemical Diagnosis through Progesterone Levels Confirmed by CYP17 Genotyping J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5739 - 5746. [Abstract] [Full Text] [PDF]

				A. Di Cerbo, A. Biason-Lauber, M. Savino, M. R. Piemontese, A. Di Giorgio, M. Perona, and A. Savoia Combined 17{alpha}-Hydroxylase/17,20-Lyase Deficiency Caused by Phe93Cys Mutation in the CYP17 Gene J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 898 - 905. [Abstract] [Full Text] [PDF]

				A. Biason-Lauber, B. Kempken, E. Werder, M. G. Forest, S. Einaudi, M. B. Ranke, N. Matsuo, V. Brunelli, E. J. Schönle, and M. Zachmann 17{alpha}-Hydroxylase/17,20-Lyase Deficiency as a Model to Study Enzymatic Activity Regulation: Role of Phosphorylation J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1226 - 1231. [Abstract] [Full Text]

				Y. Suzuki, T. Nagashima, Y. Nomura, K. Onigata, K. Nagashima, and A. Morikawa A New Compound Heterozygous Mutation (W17X, 436+5G->T) in the Cytochrome P450c17 Gene Causes 17{alpha}-Hydroxylase/17,20-Lyase Deficiency J. Clin. Endocrinol. Metab., January 1, 1998; 83(1): 199 - 202. [Abstract] [Full Text]