Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Cytochrom P450, Familie 17, Unterfamilie A, Polypeptid 1

Das CYP17A1-Gen kodiert ein Enzym, welches im endoplasmatischen Retikulum lokalisiert ist. Es ist ein SChlüsselenzym der Steroidhormonsynthese für Progesteron, Mineralocorticoide, Glucocorticoide, Androgene und Östrogene. Abhängig von der Mutation kann es zu einem isolierten Steroid-17 alpha-Hydroxylase-Mangel oder einem kombinierten 17-alpha-Hydroxylase/17,20-Lyase-Mangel kommen. Beide Erkrankungsformen sind rezessiv.

Diagnostik:

Clinic Untersuchungsmethoden Familienuntersuchung
Bearbeitungszeit 5
Probentyp genomic DNA
Research Untersuchungsmethoden Multiplex ligationsabhängige Amplifikation
Bearbeitungszeit 25
Probentyp genomic DNA
Clinic Untersuchungsmethoden Direkte Sequenzierung der proteinkodierenden Bereiche eines Gens
Bearbeitungszeit 25
Probentyp genomic DNA
Clinic Untersuchungsmethoden Hochdurchsatz-Sequenzierung
Bearbeitungszeit 25
Probentyp genomic DNA

Krankheiten:

Kongenitale adrenale Hyperplasie bei 17-alpha-Hydroxylase-Mangel
CYP17A1

Referenzen:

1.

Loukola A et al. (2004) Comprehensive evaluation of the association between prostate cancer and genotypes/haplotypes in CYP17A1, CYP3A4, and SRD5A2.

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2.

Kayes-Wandover KM et al. (2000) Steroidogenic enzyme gene expression in the human heart.

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3.

Nedelcheva Kristensen V et al. (1999) CYP17 and breast cancer risk: the polymorphism in the 5' flanking area of the gene does not influence binding to Sp-1.

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4.

Auchus RJ et al. (1999) Molecular modeling of human P450c17 (17alpha-hydroxylase/17,20-lyase): insights into reaction mechanisms and effects of mutations.

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5.

Biason-Lauber A et al. (2000) 17alpha-hydroxylase/17,20-lyase deficiency as a model to study enzymatic activity regulation: role of phosphorylation.

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6.

Wickenheisser JK et al. (2000) Differential activity of the cytochrome P450 17alpha-hydroxylase and steroidogenic acute regulatory protein gene promoters in normal and polycystic ovary syndrome theca cells.

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7.

Hanley NA et al. (2001) Expression profiles of SF-1, DAX1, and CYP17 in the human fetal adrenal gland: potential interactions in gene regulation.

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8.

Lin CJ et al. (2001) NF-1C, Sp1, and Sp3 are essential for transcription of the human gene for P450c17 (steroid 17alpha-hydroxylase/17,20 lyase) in human adrenal NCI-H295A cells.

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9.

Di Cerbo A et al. (2002) Combined 17alpha-Hydroxylase/17,20-lyase deficiency caused by Phe93Cys mutation in the CYP17 gene.

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10.

Van Den Akker EL et al. (2002) Differential inhibition of 17alpha-hydroxylase and 17,20-lyase activities by three novel missense CYP17 mutations identified in patients with P450c17 deficiency.

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11.

Gorai I et al. (2003) Estrogen-metabolizing gene polymorphisms, but not estrogen receptor-alpha gene polymorphisms, are associated with the onset of menarche in healthy postmenopausal Japanese women.

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12.

Flück CE et al. (2003) The 17, 20-lyase activity of cytochrome p450c17 from human fetal testis favors the delta5 steroidogenic pathway.

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13.

Krohn K et. al. (1992) Identification by molecular cloning of an autoantigen associated with Addison's disease as steroid 17 alpha-hydroxylase.

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14.

Martin RM et al. (2003) P450c17 deficiency in Brazilian patients: biochemical diagnosis through progesterone levels confirmed by CYP17 genotyping.

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15.

Costa-Santos M et al. (2004) 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.

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16.

Costa-Santos M et al. (2004) Two prevalent CYP17 mutations and genotype-phenotype correlations in 24 Brazilian patients with 17-hydroxylase deficiency.

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17.

Fan YS et al. (1992) Localization of the human CYP17 gene (cytochrome P450(17 alpha)) to 10q24.3 by fluorescence in situ hybridization and simultaneous chromosome banding.

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18.

Taniyama M et al. (2005) Subtle 17alpha-hydroxylase/17,20-lyase deficiency with homozygous Y201N mutation in an infertile woman.

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19.

Imai T et al. (1992) Canadian Mennonites and individuals residing in the Friesland region of The Netherlands share the same molecular basis of 17 alpha-hydroxylase deficiency.

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20.

Müssig K et al. (2005) 17alpha-hydroxylase/17,20-lyase deficiency caused by a novel homozygous mutation (Y27Stop) in the cytochrome CYP17 gene.

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21.

Hopper JL et al. (2005) A protein-truncating mutation in CYP17A1 in three sisters with early-onset breast cancer.

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22.

Jones KL et al. (1992) Male pseudohermaphroditism resulting from 17 alpha-monooxygenase (P-450C17) deficiency in two unrelated Guamanians.

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23.

Brooke AM et al. (2006) A novel point mutation in P450c17 (CYP17) causing combined 17alpha-hydroxylase/17,20-lyase deficiency.

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24.

Biason A et al. (1991) Deletion within the CYP17 gene together with insertion of foreign DNA is the cause of combined complete 17 alpha-hydroxylase/17,20-lyase deficiency in an Italian patient.

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25.

Yang J et al. (2006) Phenotype-genotype correlation in eight Chinese 17alpha-hydroxylase/17,20 lyase-deficiency patients with five novel mutations of CYP17A1 gene.

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26.

Ergun-Longmire B et al. (2006) Two novel mutations found in a patient with 17alpha-hydroxylase enzyme deficiency.

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27.

Lin D et al. (1991) Missense mutation serine106----proline causes 17 alpha-hydroxylase deficiency.

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28.

Ahlgren R et al. (1992) Compound heterozygous mutations (Arg 239----stop, Pro 342----Thr) in the CYP17 (P45017 alpha) gene lead to ambiguous external genitalia in a male patient with partial combined 17 alpha-hydroxylase/17,20-lyase deficiency.

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29.

Youngblood GL et al. (1991) Isolation, characterization, and chromosomal mapping of mouse P450 17 alpha-hydroxylase/C17-20 lyase.

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30.

Schulze JJ et al. (2008) Genetic aspects of epitestosterone formation and androgen disposition: influence of polymorphisms in CYP17 and UGT2B enzymes.

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31.

Sparkes RS et al. (1991) Regional mapping of genes encoding human steroidogenic enzymes: P450scc to 15q23-q24, adrenodoxin to 11q22; adrenodoxin reductase to 17q24-q25; and P450c17 to 10q24-q25.

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32.

Yanase T et al. (1990) Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a 7-basepair duplication in the N-terminal region of the cytochrome P45017 alpha (CYP17) gene.

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33.

Winter JS et al. (1989) Combined 17-hydroxylase and 17,20-desmolase deficiencies: evidence for synthesis of a defective cytochrome P450c17.

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34.

Kagimoto K et al. (1989) Identification of a common molecular basis for combined 17 alpha-hydroxylase/17,20-lyase deficiency in two Mennonite families.

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35.

Yanase T et al. (1989) Deletion of a phenylalanine in the N-terminal region of human cytochrome P-450(17 alpha) results in partial combined 17 alpha-hydroxylase/17,20-lyase deficiency.

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36.

Kagimoto M et al. (1988) Structural characterization of normal and mutant human steroid 17 alpha-hydroxylase genes: molecular basis of one example of combined 17 alpha-hydroxylase/17,20 lyase deficiency.

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37.

Chung BC et al. (1987) Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues.

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38.

Matteson KJ et al. (1986) Assignment of the gene for adrenal P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase) to human chromosome 10.

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39.

Yazaki K et al. (1982) Hypokalemic myopathy associated with 17 alpha-hydroxylase deficiency: a case report.

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40.

Oshiro C et al. (1995) Seventeen alpha-hydroxylase deficiency with one base pair deletion of the cytochrome P450c17 (CYP17) gene.

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41.

Carey AH et al. (1994) Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17.

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42.

Carey AH et al. (1993) Evidence for a single gene effect causing polycystic ovaries and male pattern baldness.

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43.

Laflamme N et al. (1996) Mutation R96W in cytochrome P450c17 gene causes combined 17 alpha-hydroxylase/17-20-lyase deficiency in two French Canadian patients.

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44.

Zlotogora J et al. (1996) Multiple mutations in a specific gene in a small geographic area: a common phenomenon?

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45.

Slominski A et al. (1996) ACTH receptor, CYP11A1, CYP17 and CYP21A2 genes are expressed in skin.

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46.

Miura K et al. (1996) Mutation of cytochrome P-45017 alpha gene (CYP17) in a Japanese patient previously reported as having glucocorticoid-responsive hyperaldosteronism: with a review of Japanese patients with mutations of CYP17.

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47.

Yamaguchi H et al. (1997) A 5'-splice site mutation in the cytochrome P450 steroid 17alpha-hydroxylase gene in 17alpha-hydroxylase deficiency.

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48.

Geller DH et al. (1997) The genetic and functional basis of isolated 17,20-lyase deficiency.

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49.

Suzuki Y et al. (1998) A new compound heterozygous mutation (W17X, 436 + 5G --> T) in the cytochrome P450c17 gene causes 17 alpha-hydroxylase/17,20-lyase deficiency.

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