Prevalence of Y-chromosome sequences and gonadoblastoma in Turner syndrome

A literature search was performed in Pubmed, limiting the period of time to the years 2005–2014 and using the descriptors: TS and Y sequences (n=26), and TS and Y-chromosome material (n=27). The inclusion criteria were: articles directly related to the subject and published in English or Portuguese. Articles which did not meet these criteria and review articles were excluded. After applying these criteria, 14 papers were left.

Data synthesis:

The main results regarding the prevalence of Y-chromosome sequences in TS were: (1) about 60% of the studies were conducted by Brazilian researchers; (2) the prevalence varied from 4.6 to 60%; (3) the most frequently investigated genes were SRY, DYZ3 and TSPY; (4) seven studies used only polymerase chain reaction, while in the remaining seven it was associated with FISH. Nine of the 14 studies reported gonadectomy and gonadoblastoma. The highest prevalence of gonadoblastoma (33%) was found in two studies. In five out of the nine papers evaluated the prevalence of gonadoblastoma was 10–25%; in two of them it was zero.

Conclusions:

According to these data, molecular analysis to detect Y-chromosome sequences in TS patients is indicated, regardless of their karyotype. In patients who test positive for these sequences, gonadoblastoma needs to be investigated.

KEYWORDS
Turner syndrome; Y chromosome; Gonadoblastoma; Prevalence; Polymerase chain reaction; Gonadal dysgenesis

Reference	Method(s) and Y-chromosome sequence(s) and/or probe used	n/origin	PY	Frequency
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/Brazil	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/Brazil	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/Brazil	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/Brazil	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 and PCR nested: SRY/TSPY/DYZ3	96/Brazil	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 and PCR nested: SRY/TSPY/DYZ3 ; FISH: DXZ1/DYZ3	101/Brazil	16	15.8%
Araujo 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/Brazil	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/Brazil	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/Itly	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/Turkey	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/Hungary	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/Mexico	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 ) and Yq ( sY84/sY86/sY127/sY134/sY254/sY255 ); RT-PCR: SRY/DSY14	63/Holland	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/Germany	7	11.7%

Reference	Karyotypes
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
Araujo 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

Reference	PY/P total	PG/PY	PG operated	% With gonadoblastoma	PG age (years)
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 and 19 ^a a Age at diagnosis.
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 and 19 ^a a Age at diagnosis.
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 Age at gonadectomy. ( OCT4 +: GL); 18.2 ^b b Age at gonadectomy. ( OCT4 +: GR); 17.7 ^b b Age at gonadectomy. ( OCT4 +: GR and GL)
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 and 2.8: GBB ^b b Age at gonadectomy. 15.9 and 11.6: GBM ^b b Age at gonadectomy.
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 Age at gonadectomy.
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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[1] * Corresponding author. alessandratrovo@hotmail.com (A.B.T. Marqui).