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Review

Klinefelter syndrome: clinical and molecular aspects

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Pages 765-776 | Published online: 09 Jan 2014

References

  • Klinefelter HF Jr, Reifenstein EC Jr, Albright F Jr. Syndrome characterized by gynecomastia, aspermatogenesis without a-leydigism, and increased excretion of follicle-stimulating hormone. J. Clin. Endocrinol.2(11), 615–627 (1942).
  • Bojesen A, Juul S, Gravholt CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J. Clin. Endocrinol. Metab.88(2), 622–626 (2003).
  • Bojesen A, Gravholt CH. Klinefelter syndrome in clinical practice. Nat. Clin. Pract. Urol.4(4), 192–204 (2007).
  • Wohlert M. Sex chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Birth Defects Orig. Artic. Ser.26(4), 209–223 (1990).
  • Chapple J. 47,XXY (Klinefelter syndrome) and 47,XYY: estimated rates of and indication for postnatal diagnosis with implications for prenatal counselling. Prenat. Diagn.17(4), 363–368 (1997).
  • Morris JK, Alberman E, Scott C, Jacobs P. Is the prevalence of Klinefelter syndrome increasing? Eur. J. Hum. Genet.16(2), 163–170 (2008).
  • Herlihy AS, Halliday J. Is paternal age playing a role in the changing prevalence of Klinefelter syndrome? Eur. J. Hum. Genet.16(10), 1173–1174; author reply 1174 (2008).
  • Girardin CM, Lemyre E, Alos N, Deal C, Huot C, Van Vliet G. Comparison of adolescents with Klinefelter syndrome according to the circumstances of diagnosis: amniocentesis versus clinical signs. Horm. Res.72(2), 98–105 (2009).
  • Kamischke A, Baumgardt A, Horst J, Nieschlag E. Clinical and diagnostic features of patients with suspected Klinefelter syndrome. J. Androl.24(1), 41–48 (2003).
  • Zeger MP, Zinn AR, Lahlou N et al. Effect of ascertainment and genetic features on the phenotype of Klinefelter syndrome. J. Pediatr.152(5), 716–722 (2008).
  • Smyth CM, Bremner WJ. Klinefelter syndrome. Arch. Intern. Med.158(12), 1309–1314 (1998).
  • Varrela J. Effects of X chromosome on size and shape of body: an anthropometric investigation in 47,XXY males. Am. J. Phys. Anthropol.64(3), 233–242 (1984).
  • Stemkens D, Roza T, Verrij L et al. Is there an influence of X-chromosomal imprinting on the phenotype in Klinefelter syndrome? A clinical and molecular genetic study of 61 cases. Clin. Genet.70(1), 43–48 (2006).
  • Schibler D, Brook CG, Kind HP, Zachmann M, Prader A. Growth and body proportions in 54 boys and men with Klinefelter’s syndrome. Helv. Paediatr. Acta.29(4), 325–333 (1974).
  • Brkic H, Kaic Z, Poje Z, Singer Z. Shape of the craniofacial complex in patients with Klinefelter syndrome. Angle Orthod.64(5), 371–376 (1994).
  • Brown T, Alvesalo L, Townsend GC. Craniofacial patterning in Klinefelter (47 XXY) adults. Eur. J. Orthod.15(3), 185–194 (1993).
  • Babic M, Micic M, Jaksic N, Micic S. An extra X chromosome effect on craniofacial morphogenesis in men. Eur. J. Orthod.13(4), 329–332 (1991).
  • Taheri SM, Kadir RA. Congenital diaphragmatic hernia and Klinefelter’s syndrome. J. Obstet. Gynaecol.29(8), 763–764 (2009).
  • Gautier M, Nouaille J. 2 cases of Klinefelter’s syndrome associated with a Tetralogy of Fallot (routine study of Barr’s corpuscle in 210 infants with congenital cardiopathies). Arch. Fr. Pediatr.21, 761–763 (1964).
  • Gilbert WM, Nicolaides KH. Fetal omphalocele: associated malformations and chromosomal defects. Obstet. Gynecol.70(4), 633–635 (1987).
  • Boettger MB, Kirchhof K, Sergi C, Sakmann C, Meyer P. Colobomas of the iris and choroid and high signal intensity cerebral foci on T2-weighted magnetic resonance images in Klinefelter’s syndrome. J. Pediatr. Ophthalmol. Strabismus.41(4), 247–248 (2004).
  • Lee YS, Cheng AW, Ahmed SF, Shaw NJ, Hughes IA. Genital anomalies in Klinefelter’s syndrome. Horm. Res.68(3), 150–155 (2007).
  • Ferlin A, Zuccarello D, Zuccarello B, Chirico MR, Zanon GF, Foresta C. Genetic alterations associated with cryptorchidism. JAMA.300(19), 2271–2276 (2008).
  • Gottlieb S, Rey RA, Malozowski S. Klinefelter syndrome and cryptorchidism. JAMA301(14), 1436–1437; author reply 1437 (2009).
  • Ratcliffe S. Long-term outcome in children of sex chromosome abnormalities. Arch. Dis. Child.80(2), 192–195 (1999).
  • Simpson JL, de la Cruz F, Swerdloff RS et al. Klinefelter syndrome: expanding the phenotype and identifying new research directions. Genet. Med.5(6), 460–468 (2003).
  • Wikstrom AM, Dunkel L. Testicular function in Klinefelter syndrome. Horm. Res.69(6), 317–326 (2008).
  • Bastida MG, Rey RA, Bergada I et al. Establishment of testicular endocrine function impairment during childhood and puberty in boys with Klinefelter syndrome. Clin. Endocrinol. (Oxf.)67(6), 863–870 (2007).
  • Christiansen P, Andersson AM, Skakkebaek NE. Longitudinal studies of inhibin B levels in boys and young adults with Klinefelter syndrome. J. Clin. Endocrinol. Metab.88(2), 888–891 (2003).
  • Horowitz M, Wishart JM, O’Loughlin PD, Morris HA, Need AG, Nordin BE. Osteoporosis and Klinefelter’s syndrome. Clin. Endocrinol. (Oxf.)36(1), 113–118 (1992).
  • Bojesen A, Host C, Gravholt CH. Klinefelter’s syndrome, Type 2 diabetes and the metabolic syndrome – the impact of body composition. Mol. Hum. Reprod. (2010).
  • Igawa K, Nishioka K. Leg ulcer in Klinefelter’s syndrome. J. Eur. Acad. Dermatol. Venereol.17(1), 62–64 (2003).
  • Campbell WA, Price WH. Venous thromboembolic disease in Klinefelter’s syndrome. Clin. Genet.19(4), 275–280 (1981).
  • Landwirth J, Berger A. Systemic lupus erythematosus and Klinefelter syndrome. Am. J. Dis. Child.126(6), 851–853 (1973).
  • Gomez-Raposo C, Zambrana Tevar F, Sereno Moyano M, Lopez Gomez M, Casado E. Male breast cancer. Cancer Treat. Rev. DOI:10.1016/j.ctrv.2010.02.002 (2010) (Epub ahead of print).
  • Ottesen AM, Aksglaede L, Garn I et al. Increased number of sex chromosomes affects height in a nonlinear fashion: a study of 305 patients with sex chromosome aneuploidy. Am. J. Med. Genet. A152A(5), 1206–1212 (2010).
  • Sawalha AH, Harley JB, Scofield RH. Autoimmunity and Klinefelter’s syndrome: when men have two X-chromosomes. J. Autoimmun.33(1), 31–34 (2009).
  • Scofield RH, Bruner GR, Namjou B et al. Klinefelter’s syndrome (47,XXY) in male systemic lupus erythematosus patients: support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum.58(8), 2511–2517 (2008).
  • Brinton LA, Carreon JD, Gierach GL, McGlynn KA, Gridley G. Etiologic factors for male breast cancer in the U.S. Veterans Affairs medical care system database. Breast Cancer Res. Treat.119(1), 185–192 (2010).
  • Hultborn R, Hanson C, Kopf I, Verbiene I, Warnhammar E, Weimarck A. Prevalence of Klinefelter’s syndrome in male breast cancer patients. Anticancer Res.17(6D), 4293–4297 (1997).
  • Swerdlow AJ, Schoemaker MJ, Higgins CD, Wright AF, Jacobs PA, UK Clinical Cytogenetics Group. Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study. J. Natl Cancer Inst.97(16), 1204–1210 (2005).
  • Hasle H, Jacobsen BB, Asschenfeldt P, Andersen K. Mediastinal germ cell tumour associated with Klinefelter syndrome. A report of case and review of the literature. Eur. J. Pediatr.151(10), 735–739 (1992).
  • Hasle H, Mellemgaard A, Nielsen J, Hansen J. Cancer incidence in men with Klinefelter syndrome. Br. J. Cancer.71(2), 416–420 (1995).
  • Swerdlow AJ, Higgins CD, Schoemaker MJ, Wright AF, Jacobs PA; United Kingdom Clinical Cytogenetics Group. Mortality in patients with Klinefelter syndrome in Britain: a cohort study. J. Clin. Endocrinol. Metab.90(12), 6516–6522 (2005).
  • Bojesen A, Juul S, Birkebaek N, Gravholt CH. Increased mortality in Klinefelter syndrome. J. Clin. Endocrinol. Metab.89(8), 3830–3834 (2004).
  • Bojesen A, Juul S, Birkebaek NH, Gravholt CH. Morbidity in Klinefelter syndrome: a Danish register study based on hospital discharge diagnoses. J. Clin. Endocrinol. Metab.91(4), 1254–1260 (2006).
  • Becker KL. Clinical and therapeutic experiences with Klinefelter’s syndrome. Fertil. Steril.23(8), 568–578 (1972).
  • Geschwind DH, Boone KB, Miller BL, Swerdloff RS. Neurobehavioral phenotype of Klinefelter syndrome. Ment. Retard. Dev. Disabil. Res. Rev.6(2), 107–116 (2000).
  • Steinman K, Ross J, Lai S, Reiss A, Hoeft F. Structural and functional neuroimaging in Klinefelter (47,XXY) syndrome: a review of the literature and preliminary results from a functional magnetic resonance imaging study of language. Dev. Disabil. Res. Rev.15(4), 295–308 (2009).
  • Warwick MM, Doody GA, Lawrie SM, Kestelman JN, Best JJ, Johnstone EC. Volumetric magnetic resonance imaging study of the brain in subjects with sex chromosome aneuploidies. J. Neurol. Neurosurg. Psychiatry66(5), 628–632 (1999).
  • Giedd JN, Clasen LS, Wallace GL et al. XXY (Klinefelter syndrome): a pediatric quantitative brain magnetic resonance imaging case–control study. Pediatrics.119(1), e232–e240 (2007).
  • Patwardhan AJ, Eliez S, Bender B, Linden MG, Reiss AL. Brain morphology in Klinefelter syndrome: extra X chromosome and testosterone supplementation. Neurology54(12), 2218–2223 (2000).
  • Itti E, Gaw Gonzalo IT, Pawlikowska-Haddal A et al. The structural brain correlates of cognitive deficits in adults with Klinefelter’s syndrome. J. Clin. Endocrinol. Metab.91(4), 1423–1427 (2006).
  • Itti E, Gaw Gonzalo IT, Boone KB et al. Functional neuroimaging provides evidence of anomalous cerebral laterality in adults with Klinefelter’s syndrome. Ann. Neurol.54(5), 669–673 (2003).
  • van Rijn S, Aleman A, Swaab H, Vink M, Sommer I, Kahn RS. Effects of an extra X chromosome on language lateralization: an fMRI study with Klinefelter men (47,XXY). Schizophr. Res.101(1–3), 17–25 (2008).
  • Bender BG, Puck MH, Salbenblatt JA, Robinson A. Dyslexia in 47,XXY boys identified at birth. Behav. Genet.16(3), 343–354 (1986).
  • Boada R, Janusz J, Hutaff-Lee C, Tartaglia N. The cognitive phenotype in Klinefelter syndrome: a review of the literature including genetic and hormonal factors. Dev. Disabil. Res. Rev.15(4), 284–294 (2009).
  • Ross JL, Roeltgen DP, Stefanatos G et al. Cognitive and motor development during childhood in boys with Klinefelter syndrome. Am. J. Med. Genet. A.146A(6), 708–719 (2008).
  • Bender BG, Linden MG, Robinson A. Verbal and spatial processing efficiency in 32 children with sex chromosome abnormalities. Pediatr. Res.25(6), 577–579 (1989).
  • DeLisi LE, Maurizio AM, Svetina C et al. Klinefelter’s syndrome (XXY) as a genetic model for psychotic disorders. Am. J. Med. Genet. B. Neuropsychiatr. Genet.135B(1), 15–23 (2005).
  • Bruining H, Swaab H, Kas M, van Engeland H. Psychiatric characteristics in a self-selected sample of boys with Klinefelter syndrome. Pediatrics123(5), e865–e870 (2009).
  • van Rijn S, Swaab H, Aleman A, Kahn RS. Social behavior and autism traits in a sex chromosomal disorder: Klinefelter (47XXY) syndrome. J. Autism Dev. Disord.38(9), 1634–1641 (2008).
  • van Rijn S, Aleman A, Swaab H, Kahn R. Klinefelter’s syndrome (karyotype 47,XXY) and schizophrenia-spectrum pathology. Br. J. Psychiatry.189, 459–460 (2006).
  • van Rijn S, Aleman A, Swaab H, Kahn RS. Neurobiology of emotion and high risk for schizophrenia: role of the amygdala and the X-chromosome. Neurosci. Biobehav. Rev.29(3), 385–397 (2005).
  • Jacobs PA, Strong JA. A case of human intersexuality having a possible XXY sex-determining mechanism. Nature183(4657), 302–303 (1959).
  • Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. Lancet364(9430), 273–283 (2004).
  • Visootsak J, Graham JM Jr. Klinefelter syndrome and other sex chromosomal aneuploidies. Orphanet J. Rare Dis.1, 42 (2006).
  • Stemkens D, Broekmans FJ, Kastrop PM, Hochstenbach R, Smith BG, Giltay JC. Variant Klinefelter syndrome 47,X, i(X)(q10), Y and normal 46,XY karyotype in monozygotic adult twins. Am. J. Med. Genet. A.143A(16), 1906–1911 (2007).
  • Demirhan O, Pazarbasi A, Tanriverdi N, Aridogan A, Karahan D. The clinical effects of isochromosome Xq in Klinefelter syndrome: report of a case and review of literature. Genet. Couns.20(3), 235–242 (2009).
  • Vorona E, Zitzmann M, Gromoll J, Schuring AN, Nieschlag E. Clinical, endocrinological, and epigenetic features of the 46,XX male syndrome, compared with 47,XXY Klinefelter patients. J. Clin. Endocrinol. Metab.92(9), 3458–3465 (2007).
  • Poplinski A, Wieacker P, Kliesch S, Gromoll J. Severe XIST hypomethylation clearly distinguishes (SRY+) 46,XX-maleness from Klinefelter syndrome. Eur. J. Endocrinol.162(1), 169–175 (2010).
  • Edelmann L, Hirschhorn K. Clinical utility of array CGH for the detection of chromosomal imbalances associated with mental retardation and multiple congenital anomalies. Ann. NY Acad. Sci.1151, 157–166 (2009).
  • Slavotinek AM. Novel microdeletion syndromes detected by chromosome microarrays. Hum. Genet.124(1), 1–17 (2008).
  • Maciejewski JP, Tiu RV, O’Keefe C. Application of array-based whole genome scanning technologies as a cytogenetic tool in haematological malignancies. Br. J. Haematol.146(5), 479–488 (2009).
  • Westlander G, Ekerhovd E, Granberg S, Hanson L, Hanson C, Bergh C. Testicular ultrasonography and extended chromosome analysis in men with nonmosaic Klinefelter syndrome: a prospective study of possible predictive factors for successful sperm recovery. Fertil. Steril.75(6), 1102–1105 (2001).
  • Ottesen AM, Garn ID, Aksglaede L, Juul A, Rajpert-De Meyts E. A simple screening method for detection of Klinefelter syndrome and other X-chromosome aneuploidies based on copy number of the androgen receptor gene. Mol. Hum. Reprod.13(10), 745–750 (2007).
  • Saul RA, Friez M, Eaves K et al. Fragile X syndrome detection in newborns-pilot study. Genet. Med.10(10), 714–719 (2008).
  • Thomas NS, Hassold TJ. Aberrant recombination and the origin of Klinefelter syndrome. Hum. Reprod. Update.9(4), 309–317 (2003).
  • Hall H, Hunt P, Hassold T. Meiosis and sex chromosome aneuploidy: how meiotic errors cause aneuploidy; how aneuploidy causes meiotic errors. Curr. Opin. Genet. Dev.16(3), 323–329 (2006).
  • Carothers AD, Filippi G. Klinefelter’s syndrome in Sardinia and Scotland. Comparative studies of parental age and other aetiological factors in 47,XXY. Hum. Genet.81(1), 71–75 (1988).
  • Griffin DK, Abruzzo MA, Millie EA et al. Non-disjunction in human sperm: evidence for an effect of increasing paternal age. Hum. Mol. Genet.4(12), 2227–2232 (1995).
  • Hassold TJ, Sherman SL, Pettay D, Page DC, Jacobs PA. XY chromosome nondisjunction in man is associated with diminished recombination in the pseudoautosomal region. Am. J. Hum. Genet.49(2), 253–260 (1991).
  • Eskenazi B, Wyrobek AJ, Kidd SA et al. Sperm aneuploidy in fathers of children with paternally and maternally inherited Klinefelter syndrome. Hum. Reprod.17(3), 576–583 (2002).
  • Arnedo N, Templado C, Sanchez-Blanque Y, Rajmil O, Nogues C. Sperm aneuploidy in fathers of Klinefelter’s syndrome offspring assessed by multicolour fluorescent in situ hybridization using probes for chromosomes 6, 13, 18, 21, 22, X and Y. Hum. Reprod.21(2), 524–528 (2006).
  • Skuse DH, James RS, Bishop DV et al. Evidence from Turner’s syndrome of an imprinted X-linked locus affecting cognitive function. Nature387(6634), 705–708 (1997).
  • Lorda-Sanchez I, Binkert F, Maechler M, Robinson WP, Schinzel AA. Reduced recombination and paternal age effect in Klinefelter syndrome. Hum. Genet.89(5), 524–530 (1992).
  • Zinn AR, Ramos P, Elder FF, Kowal K, Samango-Sprouse C, Ross JL. Androgen receptor CAGn repeat length influences phenotype of 47,XXY (Klinefelter) syndrome. J. Clin. Endocrinol. Metab.90(9), 5041–5046 (2005).
  • Ross MT, Grafham DV, Coffey AJ et al. The DNA sequence of the human X chromosome. Nature434(7031), 325–337 (2005).
  • Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature434(7031), 400–404 (2005).
  • Beilin J, Ball EM, Favaloro JM, Zajac JD. Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines. J. Mol. Endocrinol.25(1), 85–96 (2000).
  • Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E. X-chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients. J. Clin. Endocrinol. Metab.89(12), 6208–6217 (2004).
  • Vawter MP, Harvey PD, DeLisi LE. Dysregulation of X-linked gene expression in Klinefelter’s syndrome and association with verbal cognition. Am. J. Med. Genet. B. Neuropsychiatr. Genet.144B(6), 728–734 (2007).
  • Anagnostopoulos AK, Kolialexi A, Mavrou A et al. Proteomic analysis of amniotic fluid in pregnancies with Klinefelter syndrome foetuses. J. Proteomics73(5), 943–950 (2010).
  • Selice R, Di Mambro A, Garolla A et al. Spermatogenesis in Klinefelter syndrome. J. Endocrinol. Invest. (2010) (Epub ahead of print).
  • Laron Z, Dickerman Z, Zamir R, Galatzer A. Paternity in Klinefelter’s syndrome – a case report. Arch. Androl.8(2), 149–151 (1982).
  • Terzoli G, Lalatta F, Lobbiani A, Simoni G, Colucci G. Fertility in a 47,XXY patient: assessment of biological paternity by deoxyribonucleic acid fingerprinting. Fertil. Steril.58(4), 821–822 (1992).
  • Wikstrom AM, Raivio T, Hadziselimovic F, Wikstrom S, Tuuri T, Dunkel L. Klinefelter syndrome in adolescence: onset of puberty is associated with accelerated germ cell depletion. J. Clin. Endocrinol. Metab.89(5), 2263–2270 (2004).
  • Foresta C, Galeazzi C, Bettella A et al. Analysis of meiosis in intratesticular germ cells from subjects affected by classic Klinefelter’s syndrome. J. Clin. Endocrinol. Metab.84(10), 3807–3810 (1999).
  • Fullerton G, Hamilton M, Maheshwari A. Should non-mosaic Klinefelter syndrome men be labelled as infertile in 2009? Hum. Reprod.25(3), 588–597 (2010).
  • Ishikawa T, Nose R, Yamaguchi K, Chiba K, Fujisawa M. Learning curves of microdissection testicular sperm extraction for nonobstructive azoospermia. Fertil. Steril.94(3), :1008–1011 (2010).
  • Aksglaede L, Wikstrom AM, Rajpert-De Meyts E, Dunkel L, Skakkebaek NE, Juul A. Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum. Reprod. Update12(1), 39–48 (2006).
  • Blanco J, Egozcue J, Vidal F. Meiotic behaviour of the sex chromosomes in three patients with sex chromosome anomalies (47,XXY, mosaic 46,XY/47,XXY and 47,XYY) assessed by fluorescence in-situ hybridization. Hum. Reprod.16(5), 887–892 (2001).
  • Sciurano RB, Luna Hisano CV, Rahn MI et al. Focal spermatogenesis originates in euploid germ cells in classical Klinefelter patients. Hum. Reprod.24(9), 2353–2360 (2009).
  • Mroz K, Hassold TJ, Hunt PA. Meiotic aneuploidy in the XXY mouse: evidence that a compromised testicular environment increases the incidence of meiotic errors. Hum. Reprod.14(5), 1151–1156 (1999).
  • Bourne H, Stern K, Clarke G, Pertile M, Speirs A, Baker HW. Delivery of normal twins following the intracytoplasmic injection of spermatozoa from a patient with 47,XXY Klinefelter’s syndrome. Hum. Reprod.12(11), 2447–2450 (1997).
  • Kim SS, Garg H, Joshi A, Manjunath N. Strategies for targeted nonviral delivery of siRNAs in vivo. Trends Mol. Med.15(11), 491–500 (2009).
  • Scholefield J, Wood MJ. Therapeutic gene silencing strategies for polyglutamine disorders. Trends Genet.26(1), 29–38 (2010).
  • Jonkers I, Barakat TS, Achame EM et al. RNF12 is an X-encoded dose-dependent activator of X chromosome inactivation. Cell139(5), 999–1011 (2009).
  • Sadri-Ardekani H, Mizrak SC, van Daalen SK et al. Propagation of human spermatogonial stem cells in vitro. JAMA302(19), 2127–2134 (2009).
  • Joerg H, Janett F, Schlatt S et al. Germ cell transplantation in an azoospermic Klinefelter bull. Biol. Reprod.69(6), 1940–1944 (2003).
  • Lue Y, Liu PY, Erkkila K et al. Transplanted XY germ cells produce spermatozoa in testes of XXY mice. Int. J. Androl.33(4), 581–587 (2010).
  • Stukenborg JB, Schlatt S, Simoni M et al. New horizons for in vitro spermatogenesis? An update on novel three-dimensional culture systems as tools for meiotic and post-meiotic differentiation of testicular germ cells. Mol. Hum. Reprod.15(9), 521–529 (2009).
  • Stukenborg JB, Wistuba J, Luetjens CM et al. Coculture of spermatogonia with somatic cells in a novel three-dimensional soft-agar-culture-system. J. Androl.29(3), 312–329 (2008).
  • Neri QV, Takeuchi T, Rosenwaks Z, Palermo GD. Treatment options for impaired spermatogenesis: germ cell transplantation and stem-cell based therapy. Minerva Ginecol.61(4), 253–259 (2009).
  • Kee K, Angeles VT, Flores M, Nguyen HN, Reijo Pera RA. Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation. Nature462(7270), 222–225 (2009).
  • Wistuba J. Animal models for Klinefelter’s syndrome and their relevance for the clinic. Mol. Hum. Reprod. (2010).
  • Lewejohann L, Damm OS, Luetjens CM et al. Impaired recognition memory in male mice with a supernumerary X chromosome. Physiol. Behav.96(1), 23–29 (2009).
  • Lue Y, Jentsch JD, Wang C et al. XXY mice exhibit gonadal and behavioral phenotypes similar to Klinefelter syndrome. Endocrinology146(9), 4148–4154 (2005).
  • Wistuba J, Luetjens CM, Stukenborg JB et al. Male 41, XXY* mice as a model for Klinefelter syndrome: hyperactivation of Leydig cells. Endocrinology151(6), 2898–2910 (2010).
  • Liu PY, Kalak R, Lue Y et al. Genetic and hormonal control of bone volume, architecture and remodelling in XXY mice. J. Bone Miner. Res. DOI: 10.1002/jbmr.104 (2010) (Epub ahead of print).
  • Herlihy AS, Halliday J, McLachlan RI, Cock M, Gillam L. Assessing the risks and benefits of diagnosing genetic conditions with variable phenotypes through population screening: Klinefelter syndrome as an example. J. Commun. Genet.1, 41–46 (2010).

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