Prevalência de sequências do Y e de gonadoblastoma em síndrome de Turner

Foi feita uma pesquisa bibliográfica no Pubmed, com limite de período entre 2005 e 2014, com os descritores Turner syndrome and Y sequences (n=26) e Turner syndrome and Y chromosome material (n=27). Os critérios de inclusão foram artigos que tivessem relação direta com o tema e publicados no idioma inglês ou português. Foram excluídos aqueles que não cumpriram esses critérios e eram do tipo revisão. Após aplicação desses critérios, 14 foram selecionados.

Síntese dos dados:

Os principais resultados quanto à prevalência de sequências do cromossomo Y em síndrome de Turner foram: 1 – cerca de 60% dos estudos foram feitos por pesquisadores brasileiros; 2 – a frequência variou de 4,6 a 60%; 3 – os genes SRY, DYZ3 e TSPY foram os mais investigados; 4 – a técnica de PCR foi empregada exclusivamente em sete estudos e nos sete restantes, associada à FISH. Nove dos 14 estudos apresentaram informações sobre gonadectomia e gonadoblastoma. Dois estudos relataram a maior prevalência para gonadoblastoma (33%). Cinco dos nove estudos referiram prevalência de 10 a 25% e em dois esse valor foi nulo.

Conclusões:

De acordo com os dados apresentados, é indicada a pesquisa molecular para sequências do cromossomo Y em pacientes com ST, independentemente do cariótipo. Naquelas com positividade para essas sequências, é necessária a investigação de gonadoblastoma.

PALAVRAS-CHAVE
Síndrome de Turner; Cromossomo Y; Gonadoblastoma; Prevalência; Reação em cadeia da polimerase; Disgenesia gonadal

Referência	Método e sequência(s) do cromossomo Y e/ou sonda(s) utilizada(s)	n/Origem	PY	Frequência
Bianco et al . ⁹9 Bianco B, Lipay MV, Melaragno MI, Guedes AD, Verreschi IT. Detection of hidden Y mosaicism in Turner's syndrome: importance in the prevention of gonadoblastoma. J Pediatr Endocrinol Metab. 2006;19:1113-7.	PCR: SRY/DYZ3	20/Brasil	7	35,0%
Bianco et al . ¹⁰10 Bianco B, Lipay MV, Guedes AD, Verreschi IT. Clinical implications of the detection of Y-chromosome mosaicism in Turner's syndrome: report of 3 cases. Fertil Steril. 2008;90(1197):e17-20.	PCR: SRY/DYZ3	5/Brasil	3	60,0%
Bianco et al . ¹¹11 Bianco B, Lipay M, Guedes A, Oliveira K, Verreschi IT. SRY gene increases the risk of developing gonadoblastoma and/or nontumoral gonadal lesions in Turner syndrome. Int J Gynecol Pathol. 2009;28:197-202.	PCR: SRY/DYZ3/TSPY	87/Brasil	16	18,5%
Bianco et al . ¹²12 Bianco B, Oliveira KC, Guedes AD, Barbosa CP, Lipay MV, Verreschi IT. OCT4 gonadal gene expression related to the presence of Y-chromosome sequences in Turner syndrome. Fertil Steril. 2010;94:2347-9.	PCR: SRY/TSPY	104/Brasil	17	16,3%
Barros et al . ³3 Barros BA, Maciel-Guerra AT, De Mello MP, Coeli FB, Carvalho AB, Viguetti-Campos N, et al. A inclusão de novas técnicas de análise citogenética aperfeiçoou o diagnóstico cromossômico da síndrome de Turner. Arq Bras Endocrinol Metab. 2009;53:1137-42.	PCR e PCR nested: SRY/TSPY/DYZ3	96/Brasil	10	10,4%
Barros et al . ¹³13 Barros BA, Moraes SG, Coeli FB, Assumpção JG, De Mello MP, Maciel-Guerra AT, et al. OCT4 immunohistochemistry may be necessary to identify the real risk of gonadal tumors in patients with Turner syndrome and Y chromosome sequences. Hum Reprod. 2011;26:3450-5.	PCR e PCR nested: SRY/TSPY/DYZ3 ; FISH: DXZ1/DYZ3	101/Brasil	16	15,8%
Araújo et al . ¹⁴14 Araujo C, Galera MF, Galera BB, Silvestre FG, Medeiros SF. Molecular identification of chromosome Y sequences in Brazilian patients with Turner syndrome. Gynecol Endocrinol. 2008;24:713-7.	PCR: SRY/ZFY/DYZ1/PABY/DYS1/DYZ3	42/Brasil	2	4,8%
Bispo et al . ¹⁵15 Bispo AV, Burégio-Frota P, Oliveira dos Santos L, Leal GF, Duarte AR, Araújo J, et al. Y chromosome in Turner syndrome: detection of hidden mosaicism and the report of a rare X;Y translocation case. Reprod Fertil Dev. 2014;26:1176-82.	FISH: CEP X/CEP Y; PCR multiplex: SRY/TSPY/AMGY/DAZ	74/Brasil	5	6,8%
Mazzanti et al . ¹⁶16 Mazzanti L, Cicognani A, Baldazzi L, Bergamaschi R, Scarano E, Strocchi S, et al. Gonadoblastoma in Turner syndrome and Y-chromosome-derived material. Am J Med Genet A. 2005;135:150-4.	PCR: SRY/DYZ3; FISH: CEP 18 SA/X SG/Y SO	171/Itália	14	8,2%
Semerci et al . ¹⁷17 Semerci CN, Satiroglu-Tufan NL, Turan S, Bereket A, Tuysuz B, Yilmaz E, et al. Detection of Y chromosomal material in patients with a 45,X karyotype by PCR method. Tohoku J Exp Med. 2007;211:243-9.	PCR: PABY/SRY/DYS14/AMGY/DYZ3/DYS273/DYS280/DYS218/DYS224/DYS209/DYS231/DYS1/YRRM/DYZ1	40/Turquia	2	5,0%
Sallai et al . ¹⁸18 Sallai A, Sólyom J, Dobos M, Szabó J, Halász Z, Ságodi L, et al. Y-chromosome markers in Turner syndrome: screening of 130 patients. J Endocrinol Invest. 2010;33:222-7.	RT‐PCR: SRY/DDX3Y/HSFY1/TSPY; FISH: whole chromosome painting Y/wcp	130/Hungria	9 (RT‐PCR)	6,9%
			6 (FISH)	4,6%
Cortés‐Gutiérrez et al . ¹⁹19 Cortés-Gutiérrez EI, Herrera-Bartolo R, Dávila-Rodríguez MI, Palacios-Saucedo GC, Vargas-Villarreal J, Romero-Villarreal JB. Molecular detection of cryptic Y-chromosomal material in patients with Turner syndrome. Oncol Rep. 2012;28:1205-10.	PCR: SRY; FISH: CEP‐Y	32/México	3	9,4%
Freriks et al . ²⁰20 Freriks K, Timmers HJ, Netea-Maier RT, Beerendonk CC, Otten BJ, van Alfen-van der Velden JAEM, et al. Buccal cell FISH and blood PCR-Y detect high rates of X chromosomal mosaicism and Y chromosomal derivatives in patients with Turner syndrome. Eur J Med Genet. 2013;56:497-501.	FISH: CEP X/CEP Y/ SRY ; PCR: Yp ( SRY ) e Yq ( sY84/sY86/sY127/sY134/sY254/sY255 ); RT‐PCR: SRY/DSY14	63/Holanda	5	7,9%
Knauer‐Fischer et al . ²¹21 Knauer-Fischer S, Besikoglu B, Inta I, Kneppo C, Vogt PH, Bettendorf M. Analyses of gonadoblastoma Y (GBY)-locus and of Y centromere in Turner syndrome patients. Exp Clin Endocrinol Diabetes. 2015;123:61-5.	FISH: Ycen‐1089/1090; PCR Multiplex: Yp11 (GBY: TSPY/SRY ), Yq11 (AZFa/AZFb/AZFc)	60/Alemanha	7	11,7%

Referência	Cariótipos
Bianco et al . ⁹9 Bianco B, Lipay MV, Melaragno MI, Guedes AD, Verreschi IT. Detection of hidden Y mosaicism in Turner's syndrome: importance in the prevention of gonadoblastoma. J Pediatr Endocrinol Metab. 2006;19:1113-7.	45,X: n=7
Bianco et al . ¹⁰10 Bianco B, Lipay MV, Guedes AD, Verreschi IT. Clinical implications of the detection of Y-chromosome mosaicism in Turner's syndrome: report of 3 cases. Fertil Steril. 2008;90(1197):e17-20.	45,X/46,X,+mar: n=2; 45,X/45,X,add(15)(p11): n=1
Bianco et al . ¹¹11 Bianco B, Lipay M, Guedes A, Oliveira K, Verreschi IT. SRY gene increases the risk of developing gonadoblastoma and/or nontumoral gonadal lesions in Turner syndrome. Int J Gynecol Pathol. 2009;28:197-202.	45,X: n=12; 45,X/46,X,+mar: n=2; 45,X/45,X,add(15)(p11): n=1; 45,X/46,X,r(?): n=1
Bianco et al . ¹²12 Bianco B, Oliveira KC, Guedes AD, Barbosa CP, Lipay MV, Verreschi IT. OCT4 gonadal gene expression related to the presence of Y-chromosome sequences in Turner syndrome. Fertil Steril. 2010;94:2347-9.	45,X: n=12; 45,X/46,X,+mar: n=2; 45,X/45,X,add(15)(p11): n=1; 45,X/46,X,r(?): n=1; 45,X/47,XXX: n=1
Barros et al . ³3 Barros BA, Maciel-Guerra AT, De Mello MP, Coeli FB, Carvalho AB, Viguetti-Campos N, et al. A inclusão de novas técnicas de análise citogenética aperfeiçoou o diagnóstico cromossômico da síndrome de Turner. Arq Bras Endocrinol Metab. 2009;53:1137-42.	45,X/46,X,+mar: n=5; 45,X: n=3; 45,X/46,X,r(?): n=2
Barros et al.¹³13 Barros BA, Moraes SG, Coeli FB, Assumpção JG, De Mello MP, Maciel-Guerra AT, et al. OCT4 immunohistochemistry may be necessary to identify the real risk of gonadal tumors in patients with Turner syndrome and Y chromosome sequences. Hum Reprod. 2011;26:3450-5.	45,X: n=3; 45,X/46,XY: n=5; 45,X/46,X,+mar: n=5; 45,X/46,X,r(?): n=2; 45,X/47,XYY: n=1
Araújo et al.¹⁴14 Araujo C, Galera MF, Galera BB, Silvestre FG, Medeiros SF. Molecular identification of chromosome Y sequences in Brazilian patients with Turner syndrome. Gynecol Endocrinol. 2008;24:713-7.	45,X: n=2
Bispo et al . ¹⁵15 Bispo AV, Burégio-Frota P, Oliveira dos Santos L, Leal GF, Duarte AR, Araújo J, et al. Y chromosome in Turner syndrome: detection of hidden mosaicism and the report of a rare X;Y translocation case. Reprod Fertil Dev. 2014;26:1176-82.	45,X/46,XY: n=2; 45,X: n=1; 45,X/46,XY: n=1; 46,X,i(Xq): n=1
Mazzanti et al . ¹⁶16 Mazzanti L, Cicognani A, Baldazzi L, Bergamaschi R, Scarano E, Strocchi S, et al. Gonadoblastoma in Turner syndrome and Y-chromosome-derived material. Am J Med Genet A. 2005;135:150-4.	45,X/46,XY: n=6; 45,X: n=2; 45,X/46,X,idic(Y): n=3; 45,X/46,X,+mar: n=2; 45,X/46,XY/46,X,idic(Y): n=1
Semerci et al.¹⁷17 Semerci CN, Satiroglu-Tufan NL, Turan S, Bereket A, Tuysuz B, Yilmaz E, et al. Detection of Y chromosomal material in patients with a 45,X karyotype by PCR method. Tohoku J Exp Med. 2007;211:243-9.	45,X: n=2
Sallai et al . ¹⁸18 Sallai A, Sólyom J, Dobos M, Szabó J, Halász Z, Ságodi L, et al. Y-chromosome markers in Turner syndrome: screening of 130 patients. J Endocrinol Invest. 2010;33:222-7.	45,X: n=3; 45,X/46,XY: n=3; 45,X/46,X,+mar: n=2; 45,X/46,X,del(Xq): n=1
Cortés‐Gutiérrez et al.¹⁹19 Cortés-Gutiérrez EI, Herrera-Bartolo R, Dávila-Rodríguez MI, Palacios-Saucedo GC, Vargas-Villarreal J, Romero-Villarreal JB. Molecular detection of cryptic Y-chromosomal material in patients with Turner syndrome. Oncol Rep. 2012;28:1205-10.	45,X/46,X,+mar: n=1; 45,X/46,XY: n=1; 45,X: n=1
Freriks et al . ²⁰20 Freriks K, Timmers HJ, Netea-Maier RT, Beerendonk CC, Otten BJ, van Alfen-van der Velden JAEM, et al. Buccal cell FISH and blood PCR-Y detect high rates of X chromosomal mosaicism and Y chromosomal derivatives in patients with Turner syndrome. Eur J Med Genet. 2013;56:497-501.	45,X: n=5
Knauer‐Fischer et al . ²¹21 Knauer-Fischer S, Besikoglu B, Inta I, Kneppo C, Vogt PH, Bettendorf M. Analyses of gonadoblastoma Y (GBY)-locus and of Y centromere in Turner syndrome patients. Exp Clin Endocrinol Diabetes. 2015;123:61-5.	45,X: n=2; 45,X/46,X,idicY(q11.2): n=2; 46,X,i(X)(q10): n=1; 46,X,del(X)(q12 ou q13.1): n=1; 46,X,der(X)t(X;Y)(p22.3;q11.21): n=1

Referência	PY/P total	PG/PY	PG operadas	% com gonadoblastoma	Idade da PG (anos)
Bianco et al. ⁹9 Bianco B, Lipay MV, Melaragno MI, Guedes AD, Verreschi IT. Detection of hidden Y mosaicism in Turner's syndrome: importance in the prevention of gonadoblastoma. J Pediatr Endocrinol Metab. 2006;19:1113-7.	7/20	4/7 (57,1)	1	25,0	16
Bianco et al. ¹⁰10 Bianco B, Lipay MV, Guedes AD, Verreschi IT. Clinical implications of the detection of Y-chromosome mosaicism in Turner's syndrome: report of 3 cases. Fertil Steril. 2008;90(1197):e17-20.	3/5	3/3 (100)	0	0	–
Bianco et al. ¹¹11 Bianco B, Lipay M, Guedes A, Oliveira K, Verreschi IT. SRY gene increases the risk of developing gonadoblastoma and/or nontumoral gonadal lesions in Turner syndrome. Int J Gynecol Pathol. 2009;28:197-202.	16/87	11/16 (68,7)	2	18,2	16 e 19 ^a a Idade no diagnóstico.
Bianco et al. ¹²12 Bianco B, Oliveira KC, Guedes AD, Barbosa CP, Lipay MV, Verreschi IT. OCT4 gonadal gene expression related to the presence of Y-chromosome sequences in Turner syndrome. Fertil Steril. 2010;94:2347-9.	17/104	12/17 (70,6)	2	16,7	16 e 19 ^a a Idade no diagnóstico.
Barros et al. ¹³13 Barros BA, Moraes SG, Coeli FB, Assumpção JG, De Mello MP, Maciel-Guerra AT, et al. OCT4 immunohistochemistry may be necessary to identify the real risk of gonadal tumors in patients with Turner syndrome and Y chromosome sequences. Hum Reprod. 2011;26:3450-5.	16/101	16/16 (100)	3	18,8	15,9 ^b b Idade na gonadectomia. (OCT4 +: GE); 18,2 ^b b Idade na gonadectomia. ( OCT4 +: GD); 17,7 ^b b Idade na gonadectomia. ( OCT4 +: GD e GE)
Mazzanti et al . ¹⁶16 Mazzanti L, Cicognani A, Baldazzi L, Bergamaschi R, Scarano E, Strocchi S, et al. Gonadoblastoma in Turner syndrome and Y-chromosome-derived material. Am J Med Genet A. 2005;135:150-4.	14/171	12/14 (85,7)	4	33,3	7,64 e 2,8: GBB ^b b Idade na gonadectomia. 15,9 e 11,6: GBM ^b b Idade na gonadectomia.
Sallai et al . ¹⁸18 Sallai A, Sólyom J, Dobos M, Szabó J, Halász Z, Ságodi L, et al. Y-chromosome markers in Turner syndrome: screening of 130 patients. J Endocrinol Invest. 2010;33:222-7.	9/130	9/9 (100)	1	11,1	5,5 ^b b Idade na gonadectomia.
Cortés‐Gutiérrez et al . ¹⁹19 Cortés-Gutiérrez EI, Herrera-Bartolo R, Dávila-Rodríguez MI, Palacios-Saucedo GC, Vargas-Villarreal J, Romero-Villarreal JB. Molecular detection of cryptic Y-chromosomal material in patients with Turner syndrome. Oncol Rep. 2012;28:1205-10.	3/32	3/3 (100)	1	33,3	10
Freriks et al . ²⁰20 Freriks K, Timmers HJ, Netea-Maier RT, Beerendonk CC, Otten BJ, van Alfen-van der Velden JAEM, et al. Buccal cell FISH and blood PCR-Y detect high rates of X chromosomal mosaicism and Y chromosomal derivatives in patients with Turner syndrome. Eur J Med Genet. 2013;56:497-501.	5/63	4/5 (80)	0	0	–

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