Artículos de revistas
New Mutations, Hotspots, And Founder Effects In Brazilian Patients With Steroid 5α-reductase Deficiency Type 2
Registro en:
Journal Of Molecular Medicine. , v. 83, n. 7, p. 569 - 576, 2005.
9462716
10.1007/s00109-005-0651-7
2-s2.0-23744439831
Autor
Hackel C.
Oliveira L.E.C.
Ferraz L.F.C.
Tonini M.M.O.
Silva D.N.
Toralles M.B.
Stuchi-Perez E.G.
Guerra Jr. G.
Institución
Resumen
Mutations of the steroid 5α-reductase type 2 (SRD5A2) gene in 46,XY subjects cause masculinization defects of varying degrees, due to reduced or impaired enzymatic activity. In this study, sequence abnormalities of the SRD5A2 gene were assessed by polymerase chain reaction with specific primers and automated sequencing analysis in DNA samples from 20 patients with suspected steroid 5α-reductase type 2 deficiency from 18 Brazilian families. Eleven subjects presented SRD5A2 homozygous single-base mutations (two first cousins and four unrelated patients with G183S, two with R246W, one with del642T, one with G196S, and one with 217_218insC plus the A49T variant in heterozygosis), whereas four were compound heterozygotes (one with Q126R/IVS3+1G>A, one with Q126R/del418T, and two brothers with Q126R/G158R). Three patients were heterozygous for A207D, G196S, and R266W substitutions. The V89L polymorphism was found in heterozygosis in one of them (with A207D) and in one case with an otherwise normal gene sequence. The A49T variant was also detected in heterozygosis in the second case without other sequencing abnormalities. Four patients harbor yet non-described SRD5A2 gene mutations: a single nucleotide deletion (del642T), a G158R amino acid substitution, a splice junction mutation (IVS3+1G>A), and the insertion of a cytosine (217_218insC) occurring at a CCCC motif. This is the first report of a single-nucleotide insertion in the coding sequence of the SRD5A2 gene. In addition to these new mutations, this investigation reveals the prevalence of G183S substitution among a subset of African-Brazilian patients and presents evidences of the recurrence of already known mutations. © Springer-Verlag 2005. 83 7 569 576 Wilson, J.D., Griffin, J.E., Russell, D.W., Steroid 5 alpha-reductase 2 deficiency (1993) Endocr Rev, 14, pp. 577-593 Odame, I., Donaldson, M.D., Wallace, A.M., Cochran, W., Smith, P.J., Early diagnosis and management of 5 alpha-reductase deficiency (1992) Arch Dis Child, 67, pp. 720-723 Saenger, P., Goldman, A.S., Levine, L.S., Korth-Schutz, S., Muecke, E.C., Katsumata, M., Doberne, Y., New, M.I., Prepubertal diagnosis of steroid 5 alpha-reductase deficiency (1978) J Clin Endocrinol Metab, 46, pp. 627-634 Greene, S., Zachmann, M., Manella, B., Hesse, V., Hoepffner, W., Willgerodt, H., Prader, A., Comparison of two tests to recognize or exclude 5 alpha-reductase deficiency in prepubertal children (1987) Acta Endocrinol, 114, pp. 113-117. , Copenh Imperato-McGinley, J., Zhu, Y.S., Androgens and male physiology the syndrome of 5 alpha-reductase-2 deficiency (2002) Mol Cell Endocrinol, 198, pp. 51-59 Zucker, K.J., Intersexuality and gender identity differentiation (1999) Annu Rev Sex Res, 10, pp. 1-69 Sinnecker, G.H., Hiort, O., Dibbelt, L., Albers, N., Dorr, H.G., Hauss, H., Heinrich, U., Kruse, K., Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency (1996) Am J Med Genet, 63, pp. 223-230 Nordenskjold, A., Ivarsson, S.-A., Molecular characterization of 5 alpha-reductase type 2 deficiency and fertility in a Swedish family (1998) J Clin Endocrinol Metabol, 83, pp. 3236-3238 Human Gene Mutation Database SRD5A2 Gene, , http://uwcmml1s.uwcm.ac.uk/uwcm/mg/search/127343.html Fernandez-Cancio, M., Nistal, M., Gracia, R., Molina, M.A., Tovar, J.A., Esteban, C., Carrascosa, A., Audi, L., Compound heterozygous mutations in the SRD5A2 gene exon 4 in a male pseudohermaphrodite patient of Chinese origin (2004) J Androl, 25, pp. 412-416 Wang, Y., Li, Q., Xu, J., Liu, Q., Wang, W., Lin, Y., Ma, F., Shen, Y., Mutation analysis of five candidate genes in Chinese patients with hypospadias (2004) Eur J Hum Genet, 12, pp. 706-712 Silver, R.I., Russell, D.W., 5 alpha-reductase type 2 mutations are present in some boys with hypospadias (1999) J Urol, 162, pp. 1142-1145 Katz, M.D., Cai, L.Q., Zhu, Y., Herrera, C., DeFillo-Ricart, M., Shackleton, H.L., Imperato-McGinley, J., The biochemical and phenotypic characterization of females homozygous for 5 alpha-reductase deficiency (1995) J Clin Endocrinol Metab, 80, pp. 3160-3167 Ferraz, L.F.C., Guerra Jr., G., Baptista, M.T.M., Maciel-Guerra, A.T., Hackel, C., Detection of Gly-196-Ser mutation in 5 alpha-reductase type II gene in a Brazilian patient with female assignment and behavior (1998) J Pediatr Endocrinol Metab, 11, pp. 465-466 Ferraz, L.F.C., Baptista, M.T.M., Maciel-Guerra, A.T., Guerra Jr., G., Hackel, C., New frameshift mutation in the 5 alpha-reductase type 2 gene in a Brazilian patient with 5 alpha-reductase deficiency (1999) Am J Med Genet, 87, pp. 221-225 Bortolini, M.C., Salzano, F.M., Zago, M.A., Da Silva Jr., W.A., Weimer, T.A., Genetic variability in two Brazilian ethnic groups: A comparison of mitochondrial and protein data (1997) Am J Phys Anthropol, 103, pp. 147-156 Levy, .M.A., Brandt, M., Sheedy, K.M., Holt, D.A., Heaslip, J.I., Trill, J.J., Ryan, P.J., Bergsma, D.J., Cloning, expression and functional characterization of type 1 and type 2 steroid 5 alpha-reductases from Cynomolgus monkey: Comparisons with human and rat isoenzymes (1995) J Steroid Biochem Mol Biol, 52, pp. 307-319 Wigley, W.C., Prihoda, J.S., Mowszowicz, I., Mendonca, B.B., New, M.I., Wilson, J.D., Russell, D.W., Natural mutagenesis study of the human steroid 5 alpha-reductase 2 isozyme (1994) Biochemistry, 33, pp. 1265-1270 Mendonça, B.B., Inácio, M., Costa, E.M., Arnhold, I.J., Silva, F.A., Nicolau, W., Bloise, W., Wilson, J.D., Male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency. Diagnosis, psychological evaluation, and management (1996) Medicine, 75, pp. 64-76. , Baltimore Cai, L.Q., Zhu, Y.S., Katz, M.D., Herrera, C., Baez, J., DeFillo-Ricart, M., Shackleton, C.H., Imperato-McGinley, J., 5 alpha-reductase-2 gene mutations in the Dominican Republic (1996) J Clin Endocrinol Metab, 81, pp. 1730-1735 Weil, T.E., Black, J.K., Blutstein, H.I., Johnston, K.T., McMorris, D.S., Munson, F.P., Social System (1973) Area Handbook for the Dominican Republic, pp. 49-55. , US Government Printing Office, Superintendent of Documents, 2nd edn Russell, D.W., Wilson, J.D., Steroids 5 alpha-reductases: Two genes/two enzymes (1994) Annu Rev Biochem, 63, pp. 25-61 Boudon, C., Lumbroso, S., Lobaccaro, J.M., Szarras-Czapnik, M., Romer, T.E., Garandeau, P., Montoya, P., Sultan, C., Molecular study of the 5 alpha-reductase type 2 gene in three European families with 5α-reductase deficiency (1995) J Clin Endocrinol Metab, 80, pp. 2149-2153 Thigpen, A.E., Davis, D.I., Milatovich, A., Mendonca, B.B., Imperato-McGinley, J., Griffin, J.E., Francke, U., Russell, D.W., Molecular genetics of 5 alpha-reductase deficiency (1992) J Clin Invest, 90, pp. 799-809 Canto, P., Vilchis, F., Chavez, B., Mutchinick, O., Imperato-McGinley, J., Perez-Palacios, G., Ulloa-Aguirre, A., Mendez, J.P., Mutations of the 5 alpha-reductase type 2 gene in eight Mexican patients from six different pedigrees with 5α-reductase-2 deficiency (1997) Clin Endocrinol, 46, pp. 155-160 Makridakis, N.M., Ross, R.K., Pike, M.C., Chang, L., Stanczik, F.Z., Kolonel, L.N., Shi, C.-Y., Reichardt, J.K.V., A prevalent missense substitution that modulates activity of prostatic steroid 5 alpha-reductase (1997) Cancer Res, 57, pp. 1020-1022 Andersson, S., Berman, D.H., Jenkins, E.P., Russell, D.W., Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism (1991) Nature, 354, pp. 159-161 Hiort, O., Schütt, M.S., Bals-Pratsch, M.T., Holterhus, P.-M., Marschke, C., Struve, D., A novel homozygous disruptive mutation in the SRD5A2 gene in a partially virilized patient with 5 alpha-reductase deficiency (2002) Int J Androl, 25, pp. 55-58 Cooper, D.N., Structure and function in the human genome (1990) Human Gene Evolution, pp. 3-54. , Cooper DN (ed) BIOS Scientific, Guilford, UK Nishizawa, M., Nishizawa, K., A DNA sequence evolution analysis generalized by simulation and the Markov chain Monte Carlo method implicates strand slippage in a majority of insertions and deletions (2002) J Mol Evol, 55, pp. 706-717 Makridakis, N.M., Ross, R.K., Pike, M.C., Crocitto, L.E., Kolonel, L.N., Pearce, C.L., Henderson, B.E., Reichardt, J.K.V., A missense substitution in the SRD5A2 gene is associated with prostate cancer in African-American and Latino men in Los Angeles (1999) Lancet, 354, pp. 957-958 Allen, N.E., Reichardt, J.K.V., Nguyen, H., Key, T.J., Association between two polymorphisms in the SRD5A2 gene and serum androgen concentrations in British men (2003) Cancer Epidemiol Biomark Prev, 12, pp. 578-581 Kim, K.S., Liu, W., Cunha, G.R., Russell, D.W., Huang, H., Shapiro, E., Baskin, L.S., Expression of the androgen receptor and 5 alpha-reductase type 2 in the developing human fetal penis and urethra (2002) Cell Tissue Res, 307, pp. 145-153