Molecular diagnosis of 5α-reductase type II deficiency in Brazilian siblings with 46,XY disorder of sex development.
作者： Flávia Leme de Calais , Fernanda Caroline Soardi , Reginaldo José Petroli , Ana Letícia Gori Lusa , Roberto Benedito de Paiva e Silva
DOI: 10.3390/IJMS12129471
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摘要: The steroid 5α-reductase type II enzyme catalyzes the conversion of testosterone (T) to dihydrotestosterone (DHT), and its deficiency leads undervirilization in 46,XY individuals, due an impairment this genital tissues. Molecular analysis gene (SRD5A2) was performed two female siblings. SRD5A2 sequencing revealed that patients were homozygous for p.Gln126Arg missense mutation, which results from CGA > CAA nucleotide substitution. molecular result confirmed clinical diagnosis disorder sex development (DSD) older sister directed investigation other family members. Studies on protein structure showed severe changes at NADPH binding region indicating structural modeling can be useful evaluate deleterious role a mutation as causing deficiency.
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M. Fernández-Cancio, L. Audí, P. Andaluz, N. Torán, C. Piró, M. Albisu, M. Gussinyé, D. Yeste, M. Clemente, J. Martínez-Mora, A. Blanco, M. L. Granada, M. Marco, J. Ferragut, J. P. López-Siguero, M. Beneyto, C. Carles, A. Carrascosa, SRD5A2 gene mutations and polymorphisms in Spanish 46,XY patients with a disorder of sex differentiation. International Journal of Andrology. ,vol. 34, ,(2011) , 10.1111/J.1365-2605.2010.01136.X
Roberto Sánchez, Ursula Pieper, Francisco Melo, Narayanan Eswar, Marc A. Martí-Renom, M.S. Madhusudhan, Nebojša Mirković, Andrej Šali, Protein structure modeling for structural genomics. Nature Structural & Molecular Biology. ,vol. 7, pp. 986- 990 ,(2000) , 10.1038/80776
W. Christian Wigley, James S. Prihoda, I. Mowszowicz, Berenice B. Mendonca, Maria I. New, Jean D. Wilson, David W. Russell, Natural mutagenesis study of the human steroid 5α-reductase 2 isozyme Biochemistry. ,vol. 33, pp. 1265- 1270 ,(1994) , 10.1021/BI00171A029
Durval Damiani, Daniel Damiani, Taísa M. Ribeiro, Nuvarte Setian, [Brain sex: just beginning to pave the way]. Arquivos Brasileiros De Endocrinologia E Metabologia. ,vol. 49, pp. 37- 45 ,(2005) , 10.1590/S0004-27302005000100006
C Boudon, S Lumbroso, J M Lobaccaro, M Szarras-Czapnik, T E Romer, P Garandeau, P Montoya, C Sultan, Molecular study of the 5 alpha-reductase type 2 gene in three European families with 5 alpha-reductase deficiency. The Journal of Clinical Endocrinology and Metabolism. ,vol. 80, pp. 2149- 2153 ,(1995) , 10.1210/JCEM.80.7.7608269
Gernot H. G. Sinnecker, Olaf Hiort, Leif Dibbelt, Norbert Albers, Helmuth G. Dörr, Hannelore Hauß, Udo Heinrich, Michael Hemminghaus, Wolfgang Hoepffner, Martin Holder, Dirk Schnabel, Klaus Kruse, Phenotypic classification of male pseudohermaphroditism due to steroid 5α-reductase 2 deficiency American Journal of Medical Genetics. ,vol. 63, pp. 223- 230 ,(1996) , 10.1002/(SICI)1096-8628(19960503)63:1<223::AID-AJMG39>3.0.CO;2-O
L�cio F�bio Caldas Ferraz, Maria Teresa Mathias Baptista, Andr�a Trevas Maciel-Guerra, Gil Guerra J�nior, Christine Hackel, New frameshift mutation in the 5α-reductase type 2 gene in a Brazilian patient with 5α-reductase deficiency American Journal of Medical Genetics. ,vol. 87, pp. 221- 225 ,(1999) , 10.1002/(SICI)1096-8628(19991126)87:3<221::AID-AJMG5>3.0.CO;2-#
S Altschula, Warren Gisha, Webb Millerb, E Meyersc, D Lipmana, None, Basic Local Alignment Search Tool Journal of Molecular Biology. ,vol. 215, pp. 403- 410 ,(1990) , 10.1016/S0022-2836(05)80360-2
Stefan Andersson, David M. Berman, Elizabeth P. Jenkins, David W. Russell, Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism Nature. ,vol. 354, pp. 159- 161 ,(1991) , 10.1038/354159A0
A E Thigpen, D L Davis, A Milatovich, B B Mendonca, J Imperato-McGinley, J E Griffin, U Francke, J D Wilson, D W Russell, Molecular genetics of steroid 5α-reductase 2 deficiency Journal of Clinical Investigation. ,vol. 90, pp. 799- 809 ,(1992) , 10.1172/JCI115954