Advertisement

Chromosomal Aberrations with Endocrine Relevance (Turner Syndrome, Klinefelter Syndrome, Prader-Willi Syndrome)

  • Irén HaltrichEmail author
Chapter
Part of the Experientia Supplementum book series (EXS, volume 111)

Abstract

Turner and Klinefelter syndromes are the most common chromosome abnormalities compatible with life. Prader-Willi syndrome is a complex multisystem imprinting disorder characterized by hypothalamic dysfunction, neurological implications, and psychiatric disturbances. All three conditions are associated with progressively increasing risk for metabolic and autoimmune morbidity and mortality. This chapter focuses on the endocrine aspects of these syndromes and recent discoveries based on epigenetics and gene expression studies that have broadened our understanding of their extensive phenotypic variability and heterogeneous comorbidities.

Keywords

Turner syndrome Klinefelter syndrome Prader-Willi syndrome Autoimmune disease Hypothyroidism Infertility Chromosomal aberration Imprinting disorder Gene expression Methylation 

List of Abbreviations

AKAP17A

A-kinase anchoring protein 17A

AMOT

Angiomotin

AS

Angelman syndrome

ASD

Autism spectrum disorder

ATP10C

ATPase phospholipid transporting 10A

BMD

Bone mineral density

BP1, BP2, BP3

Breakpoint 1, 2, 3

CAI

Central adrenal insufficiency

CD99

T-cell adhesion molecule

CNR1

Cannabinoid receptor 1

CSF2RA

Colony-stimulating factor 2 receptor

CYFIP1

Cytoplasmic FMR1 interacting protein 1

DACT1

Dishevelled binding antagonist of beta catenin 1

DM

Diabetes mellitus

DOCK1, 7

Dedicator of cytokinesis 1, 7

DVT

Deep vein thrombosis

EIF2S3

Eukaryotic translation initiation factor 2 subunit gamma

FIGNL1

Fidgetin-like 1

FISH

Fluorescence in situ hybridization

FSH

Follicle-stimulating hormone

G3BP1

Stress granule assembly factor 1

GHD

Growth hormone deficiency

GH

Growth hormone

HERC2

HECT and RLD domain containing E3 ubiquitin protein ligase 2

i(X)

isoXq chromosome

IC

Imprinting center

ID

Imprinting defects

IL3RA

Receptor for interleukin-3

IVF-ET

In vitro fertilization-embryo transfer

JPX-JPX

Transcript, XIST activator

KANK1

KN motif and ankyrin repeat domains 1

KDM6A

Lysine demethylase 6A

KS

Klinefelter syndrome

LGALS1

Lectin galactoside-binding soluble 1

LH

Luteinizing hormone

M-GCTs

Mediastinal germ cell tumors

MAGEL2

MAGE family member L2

matUPD

Maternal uniparental disomy

MKRN3

Makorin ring finger protein 3

MS-MLPA

Methylation-specific multiplex-ligation probe amplification

NDN

Necdin, MAGE family member

NIPA1, 2

NIPA magnesium transporter 1, 2

NPAP1

Nuclear pore-associated protein 1

NSD1

Nuclear receptor-binding SET domain protein 1

PEX 10

Peroxisomal biogenesis factor 10

PIN4

Peptidylprolyl cis/trans isomerase, NIMA-interacting 4

POF

Premature ovarian failure

PRKX

Protein kinase X-linked

PWS

Prader-Willi syndrome

R1FM

Fragile X mental retardation 1

RPS4X

Ribosomal protein S4 X-linked

RSPO1

R-Spondin 1

SCA

Sex chromosomal aneuploidy

SHOX

Short stature homeobox

SHROOM2

Shroom family member 2

SLC25A6

Solute carrier family 25 member 6

SMARCA1

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 1

snoRNAs

Small nucleolar RNAs

SNRPN

Small nuclear ribonucleoprotein polypeptide N

SNURF

SNRPN upstream reading frame

SOX3, 9

SRY-box 3, 9

TRT

Testosterone replacement therapy

TSC22D3

TSC22 Domain family member 3

TS

Turner syndrome

TUBGCP5

Tubulin gamma complex associated protein 5

TXLNG

Taxilin gamma

UBE3A

Ubiquitin protein ligase E3A

USP9X

Ubiquitin-specific peptidase 9 X-linked

VGLL1

Vestigial-like family member 1

WNT4

Wnt family member 4

XIAP-X

Linked inhibitor of apoptosis

XIST-X

Inactive specific transcript

ZFYVE9

Zinc finger FYVE-type containing

References

  1. Abreu AP, Macedo DB, Brito VN et al (2015) A new pathway in the control of the initiation of puberty: the MKRN3 gene. J Mol Endocrinol 54:R131–R139.  https://doi.org/10.1530/JME-14-0315 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Ács OD, Péterfia B, Hollósi P et al (2018) Rapid first-tier genetic diagnosis in patients with Prader-Willi syndrome. Orv Hetil 159:64–69.  https://doi.org/10.1556/650.2018.30918 CrossRefPubMedGoogle Scholar
  3. Adam MP, Banka S, al BHT (2018) Kabuki Syndrome Medical Advisory Board Kabuki syndrome: international consensus diagnostic criteria. J Med Genet 56:89–95.  https://doi.org/10.1136/jmedgenet-2018-105625 CrossRefPubMedGoogle Scholar
  4. Angulo MA, Butler MG, Cataletto ME (2015) Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings. J Endocrinol Investig 38:1249–1263.  https://doi.org/10.1007/s40618-015-0312-9 CrossRefGoogle Scholar
  5. Bakalov VK, Cheng C, Zhou J et al (2009) X-chromosome gene dosage and the risk of diabetes in Turner syndrome. J Clin Endocrinol Metab 94:3289–3296.  https://doi.org/10.1210/jc.2009-0384 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bakalov VK, Gutin L, Cheng CM et al (2012) Autoimmune disorders in women with Turner syndrome and women with karyotypically normal primary ovarian insufficiency. J Autoimmun 38:315–321.  https://doi.org/10.1016/j.jaut.2012.01.015 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bearelly P, Oates R. (2019) Recent advances in managing and understanding Klinefelter syndrome. F1000Res 8. pii: F1000 Faculty Rev-112. doi: https://doi.org/10.12688/f1000research.16747.1 CrossRefGoogle Scholar
  8. Belling K, Russo F, Jensen AB et al (2017) Klinefelter syndrome comorbidities linked to increased X chromosome gene dosage and altered protein interactome activity. Hum Mol Genet 26:1219–1229.  https://doi.org/10.1093/hmg/ddx014 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Bianchi I, Lleo A, Gershwin ME et al (2012) The X chromosome and immune associated genes. J Autoimmun 38:J187–J192.  https://doi.org/10.1016/j.jaut.2011.11.012 CrossRefPubMedGoogle Scholar
  10. Bieth E, Eddiry S, Gaston V et al (2015) Highly restricted deletion of the SNORD116 region is implicated in Prader-Willi syndrome. Eur J Hum Genet 23:252–255.  https://doi.org/10.1038/ejhg.2014.103 CrossRefPubMedGoogle Scholar
  11. Bojesen A, Hertz JM, Gravholt CH (2011) Genotype and phenotype in Klinefelter syndrome - impact of androgen receptor polymorphism and skewed X inactivation. Int J Androl 34:e642–e648.  https://doi.org/10.1111/j.1365-2605.2011.01223.x CrossRefPubMedGoogle Scholar
  12. Borja-Santos N, Trancas B, Santos Pinto P et al (2010) 48,XXYY in a General Adult Psychiatry Department. Psychiatry (Edgmont) 7:32–36Google Scholar
  13. Bronshtein M, Zimmer EZ, Blazer S (2003) A characteristic cluster of fetal sonographic markers that are predictive of fetal Turner syndrome in early pregnancy. Am J Obstet Gynecol 188:1016–1020CrossRefGoogle Scholar
  14. Buiting K (2010) Prader-Willi syndrome and Angelman syndrome. Am J Med Genet C Semin Med Genet 154C:365–376.  https://doi.org/10.1002/ajmg.c.30273 CrossRefPubMedGoogle Scholar
  15. Butler MG, Hartin SN, Hossain WA et al (2019) Molecular genetic classification in Prader-Willi syndrome: a multisite cohort study. J Med Genet 56(3):149–153.  https://doi.org/10.1136/jmedgenet-2018-105301 CrossRefPubMedGoogle Scholar
  16. Cassidy SB, Schwartz S, Miller JL et al (2012) Prader-Willi syndrome. Genet Med 14:10–26.  https://doi.org/10.1038/gim.0b013e31822bead0 CrossRefPubMedGoogle Scholar
  17. Chai JH, Locke DP, Greally JM et al (2003) Identification of four highly conserved genes between breakpoint hotspots BP1 and BP2 of the Prader-Willi/Angelman syndromes deletion region that have undergone evolutionary transposition mediated by flanking duplicons. Am J Hum Genet 73:898–925CrossRefGoogle Scholar
  18. Chang S, Skakkebak A, Gravholt CH (2015) Klinefelter syndrome and medical treatment: hypogonadism and beyond. Hormones 14:531–548.  https://doi.org/10.14310/horm.2002.1622 CrossRefPubMedGoogle Scholar
  19. Changchien YC, Haltrich I, Micsik T et al (2012) Gonadoblastoma: case report of two young patients with isochromosome 12p found in the dysgerminoma overgrowth component in one case. Pathol Res Pract 208:628–632.  https://doi.org/10.1016/j.prp.2012.07.006 CrossRefPubMedGoogle Scholar
  20. Crinò A, Fintini D, Bocchini S et al (2018) Obesity management in Prader-Willi syndrome: current perspectives. Diabetes Metab Syndr Obes 11:579–593.  https://doi.org/10.2147/DMSO.S141352 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Davis S, Lahlou N, Bardsley M et al (2016) Gonadal function is associated with cardiometabolic health in pre-pubertal boys with Klinefelter syndrome. Andrology 4:1169–1177.  https://doi.org/10.1111/andr.12275 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Fisher EMC, Beer-Romero P, Brown LG, Ridley A, McNeil JA, Lawrence JB, Willard HF, Bieber FR, Page DC (1990) Homologous ribosomal protein genes on the human X and Y chromosomes: escape from X inactivation and possible implications for turner syndrome. Cell 63(6):1205–1218CrossRefGoogle Scholar
  23. Flori E, Biancalana V, Girard-Lemaire F, Favre R, Flori J, Doray B, Louis Mandel J (2004) Difficulties of genetic counseling and prenatal diagnosis in a consanguineous couple segregating for the same translocation (14,15) (q11;q13) and at risk for Prader–Willi and Angelman syndromes. Eur J Hum Genet 12(3):181–186CrossRefGoogle Scholar
  24. Fountain MD Jr, Schaaf CP (2015) MAGEL2 and oxytocin-implications in Prader-Willi syndrome and beyond. Biol Psychiatry 78:78–80.  https://doi.org/10.1016/j.biopsych.2015.05.006 CrossRefPubMedGoogle Scholar
  25. Frühmesser A, Kotzot D (2011) Chromosomal variants in Klinefelter syndrome. Sex Dev 5:109–123.  https://doi.org/10.1159/000327324 CrossRefPubMedGoogle Scholar
  26. Glueck CJ, Jetty V, Goldenberg N et al (2017) Thrombophilia in Klinefelter syndrome with deep venous thrombosis, pulmonary embolism, and mesenteric artery thrombosis on testosterone therapy: a pilot study. Clin Appl Thromb Hemost 23:973–979.  https://doi.org/10.1177/1076029616665923 CrossRefPubMedGoogle Scholar
  27. Gold JA, Mahmoud R, Cassidy SB et al (2018) Comparison of perinatal factors in deletion versus uniparental disomy in Prader-Willi syndrome. Am J Med Genet A 176:1161–1165.  https://doi.org/10.1002/ajmg.a.38679 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Gravholt CH, Andersen NH, Conway GS et al (2017) Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati international Turner syndrome meeting. Eur J Endocrinol 177(3):G1–G70.  https://doi.org/10.1530/EJE-17-0430 CrossRefPubMedGoogle Scholar
  29. Gravholt CH, Chang S, Wallentin M et al (2018) Klinefelter syndrome: integrating genetics, neuropsychology, and endocrinology. Endocr Rev 39:389–423.  https://doi.org/10.1210/er.2017-00212 CrossRefPubMedGoogle Scholar
  30. Green T, Flash S, Reiss AL (2019) Sex differences in psychiatric disorders: what we can learn from sex chromosome aneuploidies. Neuropsychopharmacology 44:9–21.  https://doi.org/10.1038/s41386-018-0153-2 CrossRefPubMedGoogle Scholar
  31. Gropman AL, Rogol A, Fennoy I et al (2010) Clinical variability and novel neurodevelopmental findings in 49,XXXXY syndrome. Am J Med Genet A 152A:1523–1530.  https://doi.org/10.1002/ajmg.a.33307 CrossRefPubMedGoogle Scholar
  32. Grossi A, Crinò A, Luciano R et al (2013) A. Endocrine autoimmunity in Turner syndrome. Ital J Pediatr 39:79.  https://doi.org/10.1186/1824-7288-39-79 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Grugni G, Sartorio A, Crinò A (2016) Growth hormone therapy for Prader-willi syndrome: challenges and solutions. Ther Clin Risk Manag 12:873–381.  https://doi.org/10.2147/TCRM.S70068 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Gunay-Aygun M, Schwartz S, Heeger S et al (2001) The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria. Pediatrics 108:E92CrossRefGoogle Scholar
  35. Haltrich I, Pikó H, Pamjav H et al (2015) Complex X chromosome rearrangement associated with multiorgan autoimmunity. Mol Cytogenet 8:51.  https://doi.org/10.1186/s13039-015-0152-5 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Heksch R, Kamboj M, Anglin K et al (2017) Review of Prader-Willi syndrome: the endocrine approach. Transl Pediatr 6:274–285.  https://doi.org/10.21037/tp.2017.09.04 CrossRefPubMedPubMedCentralGoogle Scholar
  37. Holm VA, Cassidy SB, Butler MG et al (1993) Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics 91:398–402PubMedPubMedCentralGoogle Scholar
  38. Houk CP, Hughes IA, Ahmed SF et al (2006) Writing Committee for the International Intersex Consensus Conference Participants. Summary of consensus statement on intersex disorders and their management. International Intersex Consensus Conference. Pediatrics 118:753–757CrossRefGoogle Scholar
  39. Jeon KC, Chen LS, Goodson P (2012) Decision to abort after a prenatal diagnosis of sex chromosome abnormality: a systematic review of the literature. Genet Med 14:27–38.  https://doi.org/10.1038/gim.0b013e31822e57a7 CrossRefPubMedGoogle Scholar
  40. Jørgensen KT, Rostgaard K, Bache I et al (2010) Autoimmune diseases in women with Turner’s syndrome. Arthritis Rheum 62:658–666.  https://doi.org/10.1002/art.27270 CrossRefPubMedGoogle Scholar
  41. Kim SJ, Miller JL, Kuipers PJ et al (2012) Unique and atypical deletions in Prader-Willi syndrome reveal distinct phenotypes. Eur J Hum Genet 20:283–290.  https://doi.org/10.1038/ejhg.2011.187 CrossRefPubMedGoogle Scholar
  42. Klinefelter HF, Reifenstein EC, Albright F (1942) Syndrome characterized by gynecomastia, spermatogenesis without A-Leydigism, and increased excretion of follicle-stimulating hormone. J Clin Endocrinol 11:615–627CrossRefGoogle Scholar
  43. Kondo T, Kuroda S, Usui K et al (2018) A case of a rare variant of Klinefelter syndrome, 47,XY,i(X)(q10). Andrologia 50:e13024.  https://doi.org/10.1111/and.13024 CrossRefPubMedGoogle Scholar
  44. Kubba H, Smyth A, Wong SC et al (2017) Ear health and hearing surveillance in girls and women with Turner’s syndrome: recommendations from the Turner’s Syndrome Support Society. Clin Otolaryngol 42:503–507.  https://doi.org/10.1111/coa.12750 CrossRefPubMedGoogle Scholar
  45. Lebenthal Y, Levy S, Sofrin-Drucker E et al (2018) The natural history of metabolic comorbidities in turner syndrome from childhood to early adulthood: comparison between 45,x monosomy and other karyotypes. Front Endocrinol 9:27.  https://doi.org/10.3389/fendo.2018.00027 CrossRefGoogle Scholar
  46. Lee MC, Conway GS (2014) Turner’s syndrome: challenges of late diagnosis. Lancet Diabetes Endocrinol 2:333–338.  https://doi.org/10.1016/S2213-8587(13)70153-0 CrossRefPubMedGoogle Scholar
  47. Liehr T, Brude E, Gillessen-Kaesbach G et al (2005) Prader-Willi syndrome with a karyotype 47,XY,+min(15)(pter->q11.1:) and maternal UPD 15-case report plus review of similar cases. Eur J Med Genet 48:175–181CrossRefGoogle Scholar
  48. Lucaccioni L, Wong SC, al SA (2015) Turner syndrome – issues to consider for transition to adulthood. Br Med Bull 113:45–58.  https://doi.org/10.1093/bmb/ldu038 CrossRefPubMedGoogle Scholar
  49. Macedo DB, Abreu AP, Reis AC (2014) Central precocious puberty that appears to be sporadic caused by paternally inherited mutations in the imprinted gene makorin ring finger 3. J Clin Endocrinol Metab 99:E1097–E1103.  https://doi.org/10.1210/jc.2013-3126 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Manzardo AM, Weisensel N, Ayala S et al (2018) Prader-Willi syndrome genetic subtypes and clinical neuropsychiatric diagnoses in residential care adults. Clin Genet 93:622–631.  https://doi.org/10.1111/cge.13142 CrossRefPubMedPubMedCentralGoogle Scholar
  51. Miller NL, Wevrick R, Mellon PL (2009) Necdin, a Prader-Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development. Hum Mol Genet 18:248–260.  https://doi.org/10.1093/hmg/ddn344 CrossRefPubMedGoogle Scholar
  52. Nieschlag E (2013) Klinefelter syndrome: the commonest form of hypogonadism, but often overlooked or untreated. Dtsch Arztebl Int 110:347–353.  https://doi.org/10.3238/arztebl.2013.0347 CrossRefPubMedPubMedCentralGoogle Scholar
  53. Ohta T, Gray TA, Rogan PK et al (1999) Imprinting mutation mechanisms in Prader-Willi syndrome. Am J Hum Genet 64:397–413CrossRefGoogle Scholar
  54. Ostergaard JR (2015) Phenotype of a child with Angelman syndrome born to a woman with Prader–Willi syndrome. Am J Med Genet Part A 167A:2138–2144.  https://doi.org/10.1002/ajmg.a.37080 CrossRefPubMedGoogle Scholar
  55. Pravdivyi I, Ballanyi K, Colmers WF et al (2015) Progressive postnatal decline in leptin sensitivity of arcuate hypothalamic neurons in the Magel2-null mouse model of Prader-Willi syndrome. Hum Mol Genet 24:4276–4278.  https://doi.org/10.1093/hmg/ddv159 CrossRefPubMedGoogle Scholar
  56. Ramsden SC, Clayton-Smith J et al (2010) Practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes. BMC Med Genet 11:70.  https://doi.org/10.1186/1471-2350-11-70 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Rappold G, Blum WF, Shavrikova EP et al (2007) Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency. J Med Genet 44:306–313CrossRefGoogle Scholar
  58. Raznahan A, Parikshak NN, Chandran V et al (2018) Sex-chromosome dosage effects on gene expression in humans. Proc Natl Acad Sci U S A 115:7398–7403.  https://doi.org/10.1073/pnas.1802889115 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Sallai A, Sólyom J, Dobos M et al (2010) Y-chromosome markers in Turner syndrome: screening of 130 patients. J Endocrinol Investig 33:222–227.  https://doi.org/10.3275/6442 CrossRefGoogle Scholar
  60. Samplaski MK, Lo KC, Grober ED et al (2014) Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients. Fertil Steril 101:950–955.  https://doi.org/10.1016/j.fertnstert.2013.12.051 CrossRefPubMedGoogle Scholar
  61. Schaaf CP, Gonzalez-Garay ML, al XF (2013) Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism. Nat Genet 45:1405–1408.  https://doi.org/10.1038/ng.2776 CrossRefPubMedPubMedCentralGoogle Scholar
  62. Seminog OO, Seminog AB, Yeates D et al (2015) Associations between Klinefelter’s syndrome and autoimmune diseases: English national record linkage studies. Autoimmunity 48:125–128.  https://doi.org/10.3109/08916934.2014.968918 CrossRefPubMedGoogle Scholar
  63. Sharma A, Jamil MA, Nuesgen N et al (2015) DNA methylation signature in peripheral blood reveals distinct characteristics of human X chromosome numerical aberrations. Clin Epigenetics 7:76.  https://doi.org/10.1186/s13148-015-0112-2 CrossRefPubMedPubMedCentralGoogle Scholar
  64. Skakkebak A, Nielsen MM, Trolle C et al (2018) DNA hypermethylation and differential gene expression associated with Klinefelter syndrome. Sci Rep 8:13740.  https://doi.org/10.1038/s41598-018-31780-0 CrossRefGoogle Scholar
  65. Sylvén L, Magnusson C, Hagenfeldt K et al (1993) Life with Turner’s syndrome-a psychosocial report from 22 middle-aged women. Acta Endocrinol 129:188–194CrossRefGoogle Scholar
  66. Tartaglia N, Davis S, Hench A et al (2008) A new look at XXYY syndrome: medical and psychological features. Am J Med Genet A 146A:1509–1522.  https://doi.org/10.1002/ajmg.a.32366 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Tartaglia N, Ayari N, Howell S et al (2011) 48,XXYY, 48,XXXY and 49,XXXXY syndromes: not just variants of Klinefelter syndrome. Acta Paediatr 100:851–860.  https://doi.org/10.1111/j.1651-2227.2011.02235.x CrossRefPubMedPubMedCentralGoogle Scholar
  68. Tian D, Sun S, Lee JT (2010) The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell 143:390–403.  https://doi.org/10.1016/j.cell.2010.09.049 CrossRefPubMedPubMedCentralGoogle Scholar
  69. Trolle C, Nielsen MM, Skakkebæk A et al (2016) Widespread DNA hypomethylation and differential gene expression in Turner syndrome. Sci Rep 30(6):34220.  https://doi.org/10.1038/srep34220 CrossRefGoogle Scholar
  70. Urbach A, Benvenisty N (2009) Studying early lethality of 45,XO (Turner’s syndrome) embryos using human embryonic stem cells. PLoS One 4:e4175.  https://doi.org/10.1371/journal.pone.0004175 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Visootsak J, Rosner B, Dykens E et al (2007) Behavioral phenotype of sex chromosome aneuploidies: 48,XXYY, 48,XXXY, and 49,XXXXY. Am J Med Genet A 143A:1198–1203CrossRefGoogle Scholar
  72. Williams LA, Pankratz N, Lane J et al (2018) Klinefelter syndrome in males with germ cell tumors: a report from the Children’s Oncology Group. Cancer 124:3900–3908.  https://doi.org/10.1002/cncr.31667 CrossRefPubMedGoogle Scholar
  73. Zinn AR, Ross JL (1998) Turner syndrome and haploinsufficiency. Curr Opin Genet Dev 8:322–327CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Faculty of Medicine, 2nd Department of PediatricsSemmelweis UniversityBudapestHungary

Personalised recommendations