Clinical and Cytogenetic Analysis of a Case of SRY-Negative XX Testicular Disorder of Sex Development
Abstract
XX testicular disorder of sex development (DSD) is a pathology that occurs in an individual with a 46,XX karyotype and an anatomical phenotype of male external genitalia, which may vary from normal to ambiguous. Clinically, two subgroups of SRY-negative and SRY-positive, 46,XX men have been described, depending on the presence of the SRY gene that is normally found on the chromosome participating in testicular determination. This article describes the personal history and clinical findings of an infant with urethral meatus abnormalities in whom a 46,XX chromosome set was identified. Also, fluorescent in situ hybridization was performed in peripheral blood lymphocytes which demonstrated the absence of the SRY gene and confirmed the presence of two X chromosomes.
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Lee P, Houk C, Ahmed S, Hughes I. Consensus statement on management of intersex disorders. International
Consensus Conference on Intersex. Pediatrics. 2006 agos.;118(2):e488-500.
https://doi.org/10.1542/peds.2006-0738
PMid:16882788
Pasterski V, Prentice P, Hughes I. Impact of the consensus statement and the new DSD classification
system. Best Pract. Res Clin Endocrinol Metab. 2010 abr.;24(2):187-95.
McClelland K, Bowles J, Koopman P. Male sex determination: Insights into molecular mechanisms. Asian
J Androl. 2012 en.;14(1):164-171.
https://doi.org/10.1038/aja.2011.169
PMid:22179516 PMCid:PMC3735148
Del Castillo V, Uranga R, Zafra G. Genética clínica. 1.ª ed. Ciudad de México: Manual Moderno; 2012. Cap. 9,
Aspectos genéticos, moleculares y celulares de la diferenciación gonadal; p. 269-280. Cap. 10, Desórdenes del desarrollo sexual; p. 281-293.
Délot E, Vilain E. Nonsyndromic 46,XX Testicular Disorders of Sex Development. [Internet]. Seatlle:
University of Washington; 2003-2015. Disponible en: http://www.ncbi.nlm.nih.gov/books/NBK1416/
Abbott Molecular. Vysis SRY Probe LSI SRY Spectrum Orange/CEP X Spectrum Green. Disponible en: https://www.molecular.abbott/us/en/chromosome/Y
Li T-F, Wu Q-Y, Zhang C, Li W-W, Zhou Q, Jiang W-J, et al. 46,XX testicular disorder of sexual development
with SRY-negative caused by some unidentified mechanisms: a case report and review of the literature. BMC Urol. 2014:14:104.
https://doi.org/10.1186/1471-2490-14-104
PMid:25529318 PMCid:PMC4289540
Sinclair A, Berta P, Palmer M, Hawkins J, Griffiths B, Smith M, et al. A gene from the human sex-determining
region encodes a protein with homology to a conserved DNA-binding motif. Nature. 1990 jul.;346(6281):240-4.
https://doi.org/10.1038/346240a0
PMid:1695712
Mittwoch U. Sex determination and sex reversal: genotype, phenotype, dogma and semantics. Hum Genet.
jul.;89(5):467-479.
Goodfellow P, Lovell R. SRY and sex determination in mammals. Annu Rev Genet. 1993;27:71-92.
https://doi.org/10.1146/annurev.ge.27.120193.000443
PMid:8122913
GeneCards. sry Gene [Internet]. Disponible en: https:// www.genecards.org/cgi-bin/carddisp.pl?gene=SRY&keywords=sry
SRY-Sex-determining region Y protein-Homo sapiens (Human)-SRY gene & protein [Internet]. Disponible en: http://www.uniprot.org/uniprot/Q05066#entry_information
Ono M, Harley V. Disorders of sex development: new genes, new concepts. Nat Rev Endocrinol. 2013 febr.;9(2):79-91.
https://doi.org/10.1038/nrendo.2012.235
PMid:23296159
Bashamboo A, McElravey K. Human sex-determination and disorders of sex- development (DSD). Semin Cell Dev Biol. 2015 sept.;45:77-83.
https://doi.org/10.1016/j.semcdb.2015.10.030
PMid:26526145
Evans HJ, Buckton KE, Spowart G, Carothers AD. Heteromorphic X chromosomes in 46,XX males: evidence
for the involvement of X-Y interchange. Hum Genet. 1979 may.;49(1):11-31.
Fechner P, Marcantonio S, Jaswaney V, Stetten G, Goodfellow P, Migeon C. The role of the sex-determining
region Y gene in the etiology of 46,XX maleness. J Clin Endocrinol Metab. 1993;76(3):690-5.
https://doi.org/10.1210/jc.76.3.690
Ergun-Longmire B, Vinci G, Alonso L, Matthew S, Tansil S, Lin-Ka K. Clinical, hormonal and cytogenetic evaluation of 46,XX malies and review of the literature. J Pediatr Endocrinol Metab. 2005 ag.;18(8):739-48.
https://doi.org/10.1515/JPEM.2005.18.8.739
PMid:16200839
Huang B, Wang S, Ning Y, Lamb A, Bartley J. Autosomal XX sex reversal caused by duplication of SOX9. Am J Med Genet. 1999 dic. 3;87(4):349-53.
https://doi.org/10.1002/(SICI)1096-8628(19991203)87:4<349::AID-AJMG13>3.0.CO;2-N
Cox J, Willatt L, Homfray T, Woods G. A SOX9 duplication and familial 46,XX developmental testicular disorder. N Engl J Med. 2011 en. 6;364:91-3.
https://doi.org/10.1056/NEJMc1010311
PMid:21208124
Temel S, Gulten T, Yakut T, Saglam H, Kilic N, Bausch E, et al.. Extended pedigree with multiple cases of XX sex reversal in the absence of SRY and of a mutation at the SOX9 locus. Sex Dev. 2007;1(1):24-34.
https://doi.org/10.1159/000096236
PMid:18391513
Grigorescu-Sido A, Heinrich U, Grigorescu P, Jauch A, Hager H, Vogt P, et al. Three new 46,XX male patients:
a clinical, cytogenetic and molecular analysis. J Pediatr Endocrinol Metab. 2005 febr.;18(2):197-203.
Chiang H, Wu Y, Wu C, Hwang J. Cytogenic and molecular analyses of 46,XX male syndrome with clinical comparison to other groups with testicular azoospermia of genetic origin. J Formos Med Assoc. 2013 febr.;112(2):72-8.
https://doi.org/10.1016/j.jfma.2012.02.009
PMid:23380608
Arboleda VA, Sandberg DE, Vilain E. DSDs: genetics, underlying pathologies and psychosexual ifferentiation.
Nat Rev Endocrinol. 2014 oct.;10(10):603-615.
https://doi.org/10.1038/nrendo.2014.130
PMid:25091731 PMCid:PMC4441533
Sutton E, Hughes J, White S, Sekido R, Tan J, Arboleda V, et al.. Identification pf SOX3 as an XX male sex reversal gene in mice and humans. J Clin Invest. 2011 en.;121(1):328- 341.
https://doi.org/10.1172/JCI42580
PMid:21183788 PMCid:PMC3007141
Kojima Y, Hayashi Y, Mizuno K, Sasaki S, Fukui Y, Koopman P, et al. Up-regulation of SOX9 in human sex-determining región on the Y chromosome (SRY)-negative XX males. Clin Endocrinol (Oxf). 2008 may.:68(5):791-9.
https://doi.org/10.1111/j.1365-2265.2007.03101.x
PMid:17986281
Refai O, Friedman A, Terry L, Jewett T, Pearlman A, Perle MA, et al. De novo 12;17 translocation upstream of SOX9 resulting in 46,XX testicular disorder of sex development. Am J Med Genet A. 2010 febr.;152A(2):422-6.
https://doi.org/10.1002/ajmg.a.33201
PMid:20082466
Polanco JC, Wilhelm D, Davidson TL, Knight D, Koopman P. Sox10 gain-of-function causes XX sex reversal in mice: implications for human 22q-linked disorders of sex development. Hum Mol Genet. 2010 febr. 1;19(3):506-516.
https://doi.org/10.1093/hmg/ddp520
PMid:19933217
Marquet F, Verloes A, Beckers A. [Clinical case of the month. A male with 46,XX karyotype]. Rev Med Liege. 1998 sept.;53(9):515-517.
Gao JL, Nie Y, Ding XP. Primed in situ labeling for detecting single-copy genes. Genet. Mol. Res. 2011 ag. 26;10(3):1884-90.
https://doi.org/10.4238/vol10-3gmr1391
PMid:21948751
Garimberti E, Tosi S. Fluorescence in situ hybridization (FISH), basic principles and methodology. Methods Mol Biol. 2010;659:3-20.
https://doi.org/10.1007/978-1-60761-789-1_1
PMid:20809300
Arboleda VA, Lee H, Sánchez FJ, Délot EC, Sandberg DE, Grody WW, et al. Targeted massively parallel sequencing provides comprehensive genetic diagnosis for patients with disorders of sex development. Clin Genet. 2013 en.; 83(1):35-43.
https://doi.org/10.1111/j.1399-0004.2012.01879.x
PMid:22435390 PMCid:PMC4052834
Hiort O, Birnbaum W, Marshall L, Wünsch L, Werner R, Schröder T, et al. Management of disorders of sex development. Nat Rev Endocrinol. 2014 sept.;10(9):520-9.
https://doi.org/10.1038/nrendo.2014.108
PMid:25022812
Barseghyan H, Délot E, Vilain E. New genomic technologies: an aid for diagnosis of disorders of sex development. Horm. Metab Res. 2015 may.;47(5):312-320.
https://doi.org/10.1055/s-0035-1548831
PMid:25970709
Baxter RM, Arboleda VA, Lee H, Barseghyan H, Adam MP, Fechner PY, et al. Exome sequencing for the diagnosis of 46,XY disorders of sex development. J Clin Endocrinol Metab. 2015 feb.;100(2):E333-44.
https://doi.org/10.1210/jc.2014-2605
PMid:25383892 PMCid:PMC4318895
Achermann JC, Domenice S, Bachega TA, Nishi MY, Mendonca BB. Disorders of sex development: effect of molecular diagnostics. Nat Rev Endocrinol. 2015 ag.;11(8):478-488.
https://doi.org/10.1038/nrendo.2015.69
PMid:25942653
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