Y chromosome in Turner syndrome
review of the literature
Keywords:
Turner syndrome, Chromosomes, human, Y, Sex cord-gonadal stromal tumors, Genes, sry, MosaicismAbstract
Turner syndrome (TS) is one of the most common types of aneuploidy among humans, and is present in 1:2000 newborns with female phenotype. Cytogenetically, the syndrome is characterized by sex chromosome monosomy (45,X), which is present in 50-60% of the cases. The other cases present mosaicism, with a 45,X cell line accompanied by one or more other cell lines with a complete or structurally abnormal X or Y chromosome. The presence of Y-chromosome material in patients with dysgenetic gonads increases the risk of gonadal tumors, especially gonadoblastoma. The greatest concern is the high risk of developing gonadoblastoma or other tumors and virilization during puberty if chromosome Y-specific sequences are present. The role of the Y chromosome in human oncogenesis is still controversial. Even though gonadoblastoma is a benign tumor, it can undergo transformation into invasive dysgerminoma in 60% of the cases, and also into other, malignant forms of germ cell tumors. Although some authors have questioned the high incidence of gonadoblastoma (around 30%), the risk of developing any kind of gonadal lesion, whether tumoral or not, justifies investigation of Y-chromosome sequences by means of the polymerase chain reaction (PCR), a highly sensitive, low-cost and easy-to-perform technique. In conclusion, mosaicism of both the X and the Y chromosome is a common finding in TS, and detection of Y-chromosome-specific sequences in patients, regardless of their karyotype, is necessary in order to prevent the development of gonadal lesions.
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Classic pages in obstetrics and gynecology by Henry H. Turner. A syndrome of infantilism, congenital webbed neck, and cubitus valgus. Endocrinology, vol. 23, pp. 566-574, 1938. Am J Obstet Gynecol. 1972;113(2):279.
Varney RF, Kenyon AT, Koch FC. An association of short stature, retarded sexual develop- ment and high urinary gonadotropin titers in women. The Journal of Clinical Endocrino- logy. 1942;2(3):137-45. Available from: http://jcem.endojournals.org/cgi/content/abstract/2/3/137. Accessed in 2009 (Nov 24).
Albright F, Smith PH, Fraser R. A syndrome characterized by primary ovarian insufficiency and decreased stature: report of 11 cases, with a digression on hormonal control of axillary and pubic hair. The American Journal of the Medical Sciences. 1942;204(5):625-48. Available from: http://journals.lww.com/amjmedsci/Citation/1942/11000/A_SYNDROME_CHARACTERIZED_BY_PRIMARY_OVARIAN.1.aspx. Accessed in 2009 (Nov 24).
Wilkins L, Fleischmann W. Ovarian agenesis. Pathology, associated clinical symptoms and the bearing on the theories of sex differentiation. The Journal of Clinical Endocrino- logy. 1944;4(8):357-75. Available from: http://jcem.endojournals.org/cgi/content/abstract/4/8/357. Accessed in 2009 (Nov 24).
Lippe B. Turner syndrome. Endocrinol Metab Clin North Am. 1991;20(1):121-52.
Gravholt CH, Juul S, Naeraa RW, Hansen J. Prenatal and postnatal prevalence of Turner’s syndrome: a registry study. BMJ. 1996;312(7022):16-21.
Ford CE, Jones KW, Polani PE, De Ameida JC, Briggs JH. A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner’s syndrome). Lancet. 1959;1(7075):711-3.
Beiguelman B. Citogenética humana. 1a ed. Rio de Janeiro: Guanabara Koogan; 1982.
Elsheikh M, Wass JA, Conway GS. Autoimmune thyroid syndrome in women with Turner’s syndrome--the association with karyotype. Clin Endocrinol (Oxf). 2001;55(2):223-6.
Gravholt CH. Epidemiological, endocrine and metabolic features in Turner syndrome. Arq Bras Endocrinol Metabol. 2005;49(1):145-56.
Vogel F, Motulsky A. Human genetics: problems and approaches. 3rd ed. London: Springer- Verlag; 1996.
Rao E, Weiss B, Fukami M, et al. Pseudoautosomal deletions encompassing a novel home- obox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet. 1997;16(1):54-63.
Gravholt CH. Epidemiological, endocrine and metabolic features in Turner syndrome. Eur J Endocrinol. 2004;151(6):657-87.
Stratakis CA, Rennert OM. Turner syndrome: molecular and cytogenetics, dysmorphology, endocrine, and other clinical manifestations and their management. The Endocrinolo- gist. 1994;4(6):442-53. Available from: http://journals.lww.com/theendocrinologist/Abstract/1994/11000/Turner_SyndromeMolecular_and_Cytogenetics,.7.aspx. Accessed in 2009 (Nov 24).
Held KR, Kerber S, Kaminsky E, et al. Mosaicism in 45,X Turner syndrome: does survi- val in early pregnancy depend on the presence of two sex chromosomes? Hum Genet. 1992;88(3):288-94.
Hook EB, Warburton D. The distribution of chromosomal genotypes associated with Turner’s syndrome: livebirth prevalence rates and evidence for diminished fetal mortality and se- verity in genotypes associated with structural X abnormalities or mosaicism. Hum Genet. 1983;64(1):24-7.
Hassold T, Benham F, Leppert M. Cytogenetic and molecular analysis of sex-chromosome monosomy. Am J Hum Genet. 1988;42(4):534-41.
Carothers AD, Frackiewicz A, De Mey R, et al. A collaborative study of the aetiology of Turner syndrome. Ann Hum Genet. 1980;43(4):355-68.
Ferguson-Smith MA, Yates JR. Maternal age specific rates for chromosome aberrations and factors influencing them: report of a collaborative european study on 52 965 amniocente- ses. Prenat Diagn. 1984 Spring;4 Spec No:5-44.
Yorifuji T, Muroi J, Kawai M, Sasaki H, Momoi T, Furusho K. PCR-based detection of mosai- cism in Turner syndrome patients. Hum Genet. 1997;99(1):62-5.
Ferguson-Smith MA. Karyotype-phenotype correlations in gonadal dysgenesis and their be- aring on the pathogenesis of malformations. J Med Genet. 1965;39:142-55.
Burgoyne PS. Mammalian sex determination: thumbs down for zinc finger? Nature. 1989;342(6252):860-2.
Fisher EM, Beer-Romero P, Brown LG, et al. Homologous ribosomal protein genes on the human X and Y chromosomes: escape from X inactivation and possible implications for Turner syndrome. Cell. 1990;63(6):1205-18.
Procter SE, Watt JL, Lloyd DJ, Duffty P. Problems of detecting mosaicism in skin. A case of trisomy 8 mosaicism illustrating the advantages of in situ tissue culture. Clin Genet. 1984;25(3):273-7.
Fernández R, Méndez J, Pásaro E. Turner syndrome: a study of chromosomal mosaicism. Hum Genet. 1996;98(1):29-35.
Quilter CR, Taylor K, Conway GS, Nathwani N, Delhanty JD. Cytogenetic and molecular inves- tigations of Y chromosome sequences and their role in Turner syndrome. Ann Hum Genet. 1998;62(Pt 2):99-106.
Hanson L, Bryman I, Barreñas ML, et al. Genetic analysis of mosaicism in 53 women with Turner syndrome. Hereditas. 2001;134(2):153-9.
Hanson L, Bryman I, Jason PO, Jakobsen AM, Hanson C. Fluorescence in situ hybridisation analysis and ovarian histology of women with Turner syndrome presenting with Y-chromo- somal material: a correlation between oral epithelial cells, lymphocytes and ovarian tissue. Hereditas. 2002;137(1):1-6.
Premi S, Srivastava J, Panneer G, Ali S. Startling mosaicism of the Y-chromosome and tan- dem duplication of the SRY and DAZ genes in patients with Turner Syndrome. PLoS One. 2008;3(11):e3796.
Nishi MY, Domenice S, Medeiros MA, Mendonca BB, Billerbeck AE. Detection of Y-specific sequences in 122 patients with Turner syndrome: nested PCR is not a reliable method. Am J Med Genet. 2002;107(4):299-305.
Lobaccaro JM, Medlej R, Berta P, et al. PCR analysis and sequencing of the SRY sex de- termining gene in four patients with bilateral congenital anorchia. Clin Endocrinol (Oxf). 1993;38(2):197-201.
López M, Canto P, Aguinaga M et al. Frequency of Y chromosomal material in Mexican pa- tients with Ullrich-Turner syndrome. Am J Med Genet. 1998;76(2):120-4.
Chu C. Y-chromosome mosaicism in girls with Turner’s syndrome. Clin Endocrinol (Oxf). 1999;50(1):17-8.
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(9):1113-17.
Nazarenko SA, Timoshevsky VA, Sukhanova NN. High frequency of tissue-specific mosaicism in Turner syndrome patients. Clin Genet. 1999;56(1):59-65.
Mendes JR, Strufaldi MW, Delcelo R, et al. Y-chromosome identification by PCR and gona- dal histopathology in Turner’s syndrome without overt Y-mosaicism. Clin Endocrinol (Oxf). 1999;50(1):19-26.
Guedes AD, Bianco B, Lipay MV, Brunoni D, de Lourdes Chauffaille M, Verreschi IT. De- termination of the sexual phenotype in a child with 45,X/46,X,Idic(Yp) mosaicism: im- portance of the relative proportion of the 45,X line in gonadal tissue. Am J Med Genet A. 2006;140A(17):1871-5.
Verp MS, Simpson JL. Abnormal sexual differentiation and neoplasia. Cancer Genet Cytoge- net. 1987;25(2):191-218.
Lipay MV, Bianco B, Verreschi IT. Disgenesias gonadais e tumores: aspectos genéticos e clí- nicos [Gonadal dysgenesis and tumors: genetic and clinical features]. Arq Bras Endocrinol Metabol. 2005;49(1):60-70.
Skakkebaek NE. Testicular dysgenesis syndrome. Horm Res. 2003;60 Suppl 3:49.
Scully RE. Gonadoblastoma. A review of 74 cases. Cancer. 1970;25(6):1340-56.
Skakkebaek NE, Holm M, Hoei-Hansen C, Jørgensen N, Rajpert-De Meyts E. Association betwe- en testicular dysgenesis syndrome (TDS) and testicular neoplasia: evidence from 20 adult pa- tients with signs of maldevelopment of the testis. APMIS. 2003;111(1):1-9; discussion 9-11.
Looijenga LH, Stoop H, de Leeuw HP, et al. POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors. Cancer Res. 2003;63(9):2244-50.
Saenger P. Clinical review 48: The current status of diagnosis and therapeutic intervention in Turner’s syndrome. J Clin Endocrinol Metab. 1993;77(2):297-301.
Hustin J, Gillerot Y, Collette J, Franchimont P. Placental alkaline phosphatase in developing normal and abnormal gonads and in germ-cell tumours. Virchows Arch A Pathol Anat Histo- pathol. 1990;417(1):67-72.
Jørgensen N, Müller J, Jaubert F, Clausen OP, Skakkebaek NE. Heterogeneity of gonado- blastoma germ cells: similarities with immature germ cells, spermatogonia and testicular carcinoma in situ cells. Histopathology. 1997;30(2):177-86.
Słowikowska-Hilczer J, Walczak-Jedrzejowska R, Kula K. Immunohistochemical diagnosis of preinvasive germ cell cancer of the testis. Folia Histochem Cytobiol. 2001;39(2):67-72.
Kocova M, Siegel SF, Wenger SL, Lee PA, Trucco M. Detection of Y chromosome se- quences in Turner’s syndrome by Southern blot analysis of amplified DNA. Lancet. 1993;342(8864):140-3.
Coto E, Toral JF, Menéndez MJ, et al. PCR-based study of the presence of Y-chromosome sequences in patients with Ullrich-Turner syndrome. Am J Med Genet. 1995;57(3):393-6.
Mancilla EE, Poggi H, Repetto G, et al. Y chromosome sequences in Turner’s syndrome: associa- tion with virilization and gonadoblastoma. J Pediatr Endocrinol Metab. 2003;16(8):1157-63.
Binder G, Koch A, Wajs E, Ranke MB. Nested polymerase chain reaction study of 53 cases with Turner’s syndrome: is cytogenetically undetected Y mosaicism common? J Clin Endocri- nol Metab. 1995;80(12):3532-6.
Osipova GR, Karmanov ME, Kozlova SI, Evgrafov OV. PCR detection of Y-specific sequences in patients with Ullrich-Turner syndrome: clinical implications and limitations. Am J Med Genet. 1998;76(4):283-7.
Damiani D, Guedes DR, Fellous M, et al. Ullrich-Turner syndrome: relevance of searching for Y chromosome fragments. J Pediatr Endocrinol Metab. 1999;12(6):827-31.
Gravholt CH, Fedder J, Naeraa RW, Müller J. Occurrence of gonadoblastoma in females with Turner syndrome and Y chromosome material: a population study. J Clin Endocrinol Metab. 2000;85(9):3199-202.
Bianco B, Lipay M, Guedes A, Oliveira K, Verreschi IT. SRY gene increases the risk of develo- ping gonadoblastoma and/or nontumoral gonadal lesions in Turner syndrome. Int J Gynecol Pathol. 2009;28(2):197-202.
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(12):713-7.
Semerci CN, Satiroglu-Tufan NL, Turan S, et al. Detection of Y chromosomal material in patients with a 45,X karyotype by PCR method. Tohoku J Exp Med. 2007;211(3):243-9.
Harley VR, Clarkson MJ, Argentaro A. The molecular action and regulation of the testis-deter- mining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9]. Endocr Rev. 2003;24(4):466-87.
Tsuchiya K, Reijo R, Page DC, Disteche CM. Gonadoblastoma: molecular definition of the susceptibility region on the Y chromosome. Am J Hum Genet. 1995;57(6):1400-7.
Page DC. Hypothesis: a Y-chromosomal gene causes gonadoblastoma in dysgenetic gonads. Development. 1987;101 Suppl:151-5.
Salo P, Kääriäinen H, Petrovic V, Peltomäki P, Page DC, de la Chapelle A. Molecular mapping of the putative gonadoblastoma locus on the Y chromosome. Genes Chromosomes Cancer. 1995;14(3):210-4.
Hildenbrand R, Schröder W, Brude E, et al. Detection of TSPY protein in a unilateral micros- copic gonadoblastoma of a Turner mosaic patient with a Y-derived marker chromosome. J Pathol. 1999;189(4):623-6.
Schöler HR, Dressler GR, Balling R, Rohdewohld H, Gruss P. Oct-4: a germline-specific trans- cription factor mapping to the mouse t-complex. EMBO J. 1990;9(7):2185-95.
Okamoto K, Okazawa H, Okuda A, Sakai M, Muramatsu M, Hamada H. A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells. Cell. 1990;60(3):461-72.
Rosner MH, Vigano MA, Ozato K, et al. A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature. 1990;345(6277):686-92.
Pera MF, Herszfeld D. Differentiation of human pluripotent teratocarcinoma stem cells indu- ced by bone morphogenetic protein-2. Reprod Fertil Dev. 1998;10(7-8):551-5.
Goto T, Adjaye J, Rodeck CH, Monk M. Identification of genes expressed in human primordial germ cells at the time of entry of the female germ line into meiosis. Mol Hum Reprod. 1999;5(9):851-60.
Hansis C, Grifo JA, Krey LC. Oct-4 expression in inner cell mass and trophectoderm of human blastocysts. Mol Hum Reprod. 2000;6(11):999-1004.
Ramos ES. Turner syndrome: counseling prior to oocyte donation. Sao Paulo Med J. 2007;125(2):112-4.
Rosen GF, Kaplan B, Lobo RA. Menstrual function and hirsutism in patients with gonadal dysgenesis. Obstet Gynecol. 1988;71(5):677-80.
Cabanas P, García-Caballero T, Barreiro J, et al. Papillary thyroid carcinoma after recombi- nant GH therapy for Turner syndrome. Eur J Endocrinol. 2005;153(4):499-502.
Saenger P, Wikland KA, Conway GS, et al. Recommendations for the diagnosis and manage- ment of Turner syndrome. J Clin Endocrinol Metab. 2001;86(7):3061-9.
Frías JL, Davenport ML; Committee on Genetics and Section on Endocrinology.. Health su- pervision for children with Turner syndrome. Pediatrics. 2003;111(3):692-702.
Canto P, Kofman-Alfaro S, Jiménez AL, et al. Gonadoblastoma in Turner syndrome patients with nonmosaic 45,X karyotype and Y chromosome sequences. Cancer Genet Cytogenet. 2004;150(1):70-2.
