Osman DEMİRHAN, Nilgün TANRIVERDİ, Ayfer PAZARBAŞI, Dilara SÜLEYMANOVA

Frequencies and distributions of sex chromosome abnormalities in females with the Turner phenotype: a long-term retrospective study in the southern region of Turkey

Background/aim:The genetic background of Turner syndrome (TS) is highly variable. The correlation between genotype and phenotype is not yet well understood. The aim of this study was to describe the frequencies and distributions of Turner karyotypes and to discuss the phenotype/genotype relation in a very large group of individuals with TS. Materials and methods: The karyotype results of 248 female participants were evaluated retrospectively. Results: Of 248 females with the Turner phenotype, 14.5% had normal karyotypes and 85.5% had Turner karyotypes. About 72.2% of the abnormalities were numerical aberrations and 27.8% were structural aberrations. The most frequent karyotype was monosomy X, which was found in 135 females (63.7%), followed by 44 mosaics (21%), 40 isochromosomes of the long and short arms of chromosome X (19.1%), and 17 deletions of the short and long arms of chromosome X (8.0%). One case of Robertsonian translocation and one case of mosaic TS with marker chromosome were detected. Conclusion: This study shows the frequency and distribution of karyotypes in females with TS. There is great value to be gleaned from studies of females with TS in furthering our understanding of the atypical clinical features associated with TS. Studies involving genetic analyses will be necessary to examine gene expression profiles in girls with TS and identify potential candidate genes underlying the atypical clinical features associated with TS.

PDF

___

1. Ford CE, Jones KW, Polani PE, Almeida JC, Briggs, JH. A sexchromosome anomaly in a case of gonadal dysgenesis (Turners syndrome). Lancet 1959; 1: 711-713.
2. Urbach A, Benvenisty N. Studying early lethality of 45,XO (Turners syndrome) embryos using human embryonic stem cells. PLoS One 2009; 4: e4175.
3. Mohamed AE, Mahmoud NK. Axenfeld-Rieger spectrum in a patient with 45,X Turner syndrome. Ophthalmic Genet 2012; 33: 111-115.
4. Pazarbaşı A, Demirhan O, Taşdemir D, Tunç E, Tuncay Özgünen F, Alptekin D, Evrüke C, Demir C, Kasap M, Karakan Karakaş Z et al. Evaluation of the cytogenetical results of 4707 cases diagnosed with amniocentesis. Cukurova Med J 2011; 36: 8-14.
5. Gravholt CH, Juul S, Naeraa RW, Hansen J. Prenatal and postnatal prevalence of Turners syndrome: a registry study. BMJ 1996; 312: 16-21.
6. Larsen T, Gravholt CH, Tillebeck A, Larsen H, Jensen MB, Nielsen J, Friedrich U. Parental origin of the X chromosome, X chromosome mosaicism and screening for hidden Y chromosome in 45,X Turner syndrome ascertained cytogenetically. Clin Genet 1995; 48: 6-11.
7. Jacobs PA, Betts PR, Cockwell AE, Crolla JA, Mackenzie MJ, Robinson DO, Youings SA. A cytogenetic and molecular reappraisal of a series of patients with Turners syndrome. Ann Hum Genet 1990; 54: 209-23.
8. Bondy CA, Matura LA, Wooten N, Troendle J, Zinn AR, Bakalov VK. The physical phenotype of girls and women with Turner syndrome is not X-imprinted. Hum Genet 2007; 121: 469-474.
9. Ross J, Roeltgen D, Zinn A. Cognition and the sex chromosomes: studies in Turner syndrome. Horm Res 2006; 65: 47-56.
10. Ross J, Zinn A, McCauley E. Neurodevelopmental and psychosocial aspects of Turner syndrome. Ment Retard Dev Disabil Res Rev 2000; 6: 135-141.
11. Zinn AR, Roeltgen D, Stefanatos G, Ramos P, Elder FF, Kushner H, Kowal K, Ross JL. A Turner syndrome neurocognitive phenotype maps to Xp22.3. Behav Brain Funct 2007; 3: 24-38.
12. Kocova M, Siegel SF, Wenger SL, Lee PA, Nalesnik M, Trucco M. Detection of Y chromosome sequences in a 45,X/46,XXqpatient by Southern blot analysis of PCR-amplified DNA and fluorescent in situ hybridization (FISH). Am J Med Genet 1995; 55: 483-488.
13. Ogata T, Muroya K, Matsuo N, Shinohara O, Yorifuji T, Nishi Y, Hasegawa Y, Horikawa R, Tachibana K. Turner syndrome and Xp deletions: clinical and molecular studies in 47 patients. J Clin Endocrinol Metab 2001; 86: 5498-5508.
14. Chang HJ, Clark RD, Bachman H. The phenotype of 45,X/46,XY mosaicism: an analysis of 92 prenatally diagnosed cases. Am J Hum Genet 1990; 46: 156-167.
15. Wheeler M, Peakman D, Robinson A, Henry G. 45,X/46,XY mosaicism: contrast of prenatal and postnatal diagnosis. Am J Med Genet 1998; 29: 565-571.
16. Davenport ML. Approach to the patient with Turner syndrome. J Clin Endocrinol Metab 2010; 95: 1487-1495.
17. Zinn AR, Tonk VS, Chen Z, Flejter WL, Gardner HA, Guerra R, Kushner H, Schwartz S, Sybert VP, Van-Dyke DL et al. Evidence for a Turner syndrome locus or loci at Xp11.2-p22.1. Am J Hum Genet 1998; 63: 1757-1766.
18. Barlow DP. Gametic imprinting in mammals. Science 1998; 270: 1610-1613.
19. Constancia M, Pickard B, Kelsey G, Reik W. Imprinting mechanisms. Genome Res 1998; 8: 881-900.
20. Brown WE, Kesler SR, Eliez S, Warsofsky IS, Haberecht M, Patwardhan A, Ross JL, Neely EK, Zeng SM, Yankowitz J et al. Brain development in Turner syndrome: a magnetic resonance imaging study. Psychiatry Res Neuroimaging 2002; 116: 187-196.
21. Kesler SR, Blasey CM, Brown WE, Yankowitz J, Zeng SM, Bender BG, Reiss AL. Effects of X-monosomy and X-linked imprinting on superior temporal gyrus morphology in Turner syndrome. Biol Psychiatry 2003; 54: 636-646.
22. Larizza D, Maraschio P, Bardoni B, Calcaterra V, Manfredi P, Gemma A. Two sisters with 45,X karyotype: influence of genomic imprinting on phenotype and cognitive profile. Eur J Pediatr 2002; 161: 224-225.
23. Skuse DH. X-linked genes and mental functioning. Hum Mol Genet 2005; 14: R27-R32.
24. Loesch DZ, Bui QM, Kelso W, Huggins RM, Slater H, Warne G, Bergman PB, Rodda C, Mitchell RJ, Prior M et al. Effect of Turners syndrome and X-linked imprinting on cognitive status: analysis based on pedigree data. Brain Dev 2005; 27: 494-503.
25. Bishop DV, Canning E, Elgar K, Morris E, Jacobs PA, Skuse DH. Distinctive patterns of memory function in subgroups of females with Turner syndrome: evidence for imprinted loci on the X-chromosome affecting neurodevelopment. Neuropsychologia 2000; 38: 712-721.
26. Savendahl L, Davenport ML. Delayed diagnoses of Turners syndrome: proposed guidelines for change. J Pediatr 2000; 137: 455-459.
27. Huang B, Thangavelu M, Bhatt S, J Sandlin C, Wang S. Prenatal diagnosis of 45,X and 45,X mosaicism: the need for thorough cytogenetic and clinical evaluations. Prenat Diagn 2002; 22: 105-110.
28. Ruiz C, Lamm F, Hart PS. Turner syndrome and multiplemarker screening. Clin Chem 1999; 45: 2259-2261.
29. Jacobs PA, Hassold TJ. The origin of numerical chromosome abnormalities. Adv Genet 1995; 33: 101-133.
30. Monroy N, Lopez M, Cervantes A, Garcia-Cruz D, Zafra G, Canun S, Zenteno JC, Kofman-Alfaro S. Microsatellite analysis in Turner syndrome: parental origin of X chromosomes and possible mechanism of formation of abnormal chromosomes. Am J Med Genet 2002; 107: 181-189.
31. Uematsu A, Yorifuji T, Muroi J, Kawai M, Mamada M, Kaji M, Yamanaka C, Momoi T, Nakahata T. Parental origin of normal X chromosomes in Turner syndrome patients with various karyotypes: implications for the mechanism leading to generation of a 45,X karyotype. Am J Med Genet 2002; 111: 134-139.
32. Jacobs P, Dalton P, James R, Mosse K, Power M, Robinson D, Skuse D. Turner syndrome: a cytogenetic and molecular study. Ann Hum Genet 1997; 61: 471-483.
33. Hildenbrand R, Schröder W, Brude E. Detection of TSPY protein in a unilateral microscopic gonadoblastoma of a Turner mosaic patient with a Y-derived marker chromosome. J Pathol 1999; 189: 623-626.
34. Gotzsche CO, Krag-Olsen B, Nielsen J, Sorensen KE, Kristensen BO. Prevalence of cardiovascular malformations and association with karyotypes in Turners syndrome. Arch Dis Child 1994; 71: 433-436.
35. Mazzanti L, Cacciari E. Congenital heart disease in patients with Turners syndrome. Italian Study Group for Turner Syndrome (ISGTS). J Pediatr 1998; 133: 688-692.
36. Miller MJ, Geffner ME, Lippe BM, Itami RM, Kaplan SA, DiSessa TG, Isabel-Jones JB, Friedman WF. Echocardiography reveals a high incidence of bicuspid aortic valve in Turner syndrome. J Pediatr 1983; 102: 47-50.
37. Murphy DG, Allen G, Haxby JV, Largay KA, Daly E, White BJ, Powell CM, Schapiro MB. The effects of sex steroids, and the X chromosome, on female brain function: a study of the neuropsychology of adult Turner syndrome. Neuropsychologia 1994; 32: 1309-1323.
38. McCauley E, Kay T, Ito J, Treder R. The Turner syndrome: cognitive deficits, affective discrimination, and behavior problems. Child Dev 1987; 58: 464-473.
39. Hook EB, Warburton D. The distribution of chromosomal genotypes associated with Turners syndrome: livebirth prevalence rates and evidence for diminished fetal mortality and severity in genotypes associated with structural X abnormalities or mosaicism. Hum Genet 1983; 64: 24-27.
40. Jones KL. Smiths Recognizable Patterns of Human Malformations. 5th ed. New York, NY, USA: W.B. Saunders Company; 1997.
41. Ostrer H, Clayton CM. Y chromosome mosaicism in 45,X Turner syndrome. Am J Med Genet 1989; 34: 294-296.
42. Coto E, Toral JF, Menendez MJ, Hernando I, Plasencia A, Benavides A, Lopez-Larrea C. PCR-based study of the presence of Y chromosome sequences in patients with Ullrich-Turner syndrome. Am J Med Genet 1995; 57: 393-396.
43. Salo P, Kaariainen H, Petrovic V, Peltomaki P, Page DC, de la Chapelle A. Molecular mapping of the putative gonadoblastoma locus on the Y chromosome. Genes Chromosomes Cancer 1995; 14: 210-214.
44. 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: 1400-1407.
45. Ranke MB, Saenger P. Turners syndrome. Lancet 2001; 358: 309-314.
46. Elsheikh M, Dunger DB, Conway GS, Wass JA. Turners syndrome in adulthood. Endocr Rev 2002; 23: 120-140.
47. Sybert VP. Turner syndrome. In: Cassidy SB, Allanson JE, editors. Management of Genetic Syndromes. New York, NY, USA: Wiley-Liss, 2001. pp. 459-484.
48. Elsheikh M, Wass JA, Conway GS. Autoimmune thyroid syndrome in women with Turners syndrome the association with karyotype. Clin Endocrinol (Oxf ) 2001; 55: 223-226.
49. Davison RM, Davis CJ, Conway GS. The X chromosome and ovarian failure. Clin Endocrinol (Oxf) 1999; 51: 673-679.
50. Carrel L, Cottle AA, Goglin KC, Willard HF. A first-generation X-inactivation profile of the human X chromosome. P Natl Acad Sci USA 1999; 96: 14440-14444.