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. 2019 Apr;21(4):877-886.
doi: 10.1038/s41436-018-0271-6. Epub 2018 Sep 5.

Mosaic Turner syndrome shows reduced penetrance in an adult population study

Marcus A Tuke  1 , Katherine S Ruth  1 , Andrew R Wood  1 , Robin N Beaumont  1 , Jessica Tyrrell  1 , Samuel E Jones  1 , Hanieh Yaghootkar  1 , Claire L S Turner  2 , Mollie E Donohoe  3 , Antonia M Brooke  3 , Morag N Collinson  4 , Rachel M Freathy  1 , Michael N Weedon  1 , Timothy M Frayling  1 , Anna Murray  5
Affiliations

Mosaic Turner syndrome shows reduced penetrance in an adult population study

Marcus A Tuke et al. Genet Med. 2019 Apr.

Abstract

Purpose: Many women with X chromosome aneuploidy undergo lifetime clinical monitoring for possible complications. However, ascertainment of cases in the clinic may mean that the penetrance has been overestimated.

Methods: We characterized the prevalence and phenotypic consequences of X chromosome aneuploidy in a population of 244,848 women over 40 years of age from UK Biobank, using single-nucleotide polymorphism (SNP) array data.

Results: We detected 30 women with 45,X; 186 with mosaic 45,X/46,XX; and 110 with 47,XXX. The prevalence of nonmosaic 45,X (12/100,000) and 47,XXX (45/100,000) was lower than expected, but was higher for mosaic 45,X/46,XX (76/100,000). The characteristics of women with 45,X were consistent with the characteristics of a clinically recognized Turner syndrome phenotype, including short stature and primary amenorrhea. In contrast, women with mosaic 45,X/46,XX were less short, had a normal reproductive lifespan and birth rate, and no reported cardiovascular complications. The phenotype of women with 47,XXX included taller stature (5.3 cm; SD = 5.52 cm; P = 5.8 × 10-20) and earlier menopause age (5.12 years; SD = 5.1 years; P = 1.2 × 10-14).

Conclusion: Our results suggest that the clinical management of women with 45,X/46,XX mosaicism should be minimal, particularly those identified incidentally.

Keywords: Turner syndrome; aneuploidy; mosaicism; trisomy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Exemplar log R ratio (LRR) and B-allele frequency (BAF) plots for each detected X chromosome state. (a,b) Respective LRR and BAF for a >80% dosage 45,X individual. (c,d) LRR and BAF for a mosaic (≤80%) dosage 45,X/46,XX individual respectively. (e,f) Respective LRR and BAF of a 46,XX individual. (g,h) Respective LRR and BAF of a 47,XXX individual. Finally for comparison, plots (i) and (j) represent the respective LRR and BAF of a 46,XY male illustrating a similar LRR dosage to 45,X; note the 4.5-Mb 2-copy dosage region at 88.5 Mb on chromosome X, which is homologous to the Y chromosome present in all males (PAR3)
Fig. 2
Fig. 2. Relationship between chromosome X dosage in 45, X and 47, XXX females for two quantitative traits.
(a) Shows the height of 45, X and 47, XXX females in UK Biobank and (b) Shows the natural menopause age 45, X and 47, XXX females in UK Biobank. X chromosome dosage is color coded (see key) for each category tested in the analysis. Distribution of each trait in controls is shown in gray histogram for (a) height and (b) natural menopause age
See this image and copyright information in PMC

Comment in

  • Response to Prakash et al.
    Tuke MA, Ruth KS, Wood AR, Beaumont RN, Tyrrell J, Jones SE, Yaghootkar H, Turner CLS, Donohoe ME, Brooke AM, Collinson MN, Freathy RM, Weedon MN, Frayling TM, Murray A. Tuke MA, et al. Genet Med. 2019 Aug;21(8):1884-1885. doi: 10.1038/s41436-018-0412-y. Epub 2018 Dec 21. Genet Med. 2019. PMID: 30573795 No abstract available.
  • 45,X mosaicism in a population-based biobank: implications for Turner syndrome.
    Prakash SK, Crenshaw ML, Backeljauw PF, Silberbach M, Scurlock C, Culin DD, Ranallo KC, Lin AE. Prakash SK, et al. Genet Med. 2019 Aug;21(8):1882-1883. doi: 10.1038/s41436-018-0411-z. Epub 2018 Dec 21. Genet Med. 2019. PMID: 30573796 No abstract available.

References

    1. Otter M, Schrander-Stumpel CT, Curfs LM. Triple X syndrome: a review of the literature. Eur J Hum Genet. 2010;18:265–271. doi: 10.1038/ejhg.2009.109. - DOI - PMC - PubMed
    1. Tokita MJ, Sybert VP. Postnatal outcomes of prenatally diagnosed 45,X/46,XX. Am J Med Genet A. 2016;170a:1196–1201. doi: 10.1002/ajmg.a.37551. - DOI - PubMed
    1. Viuff MH, Stochholm K, Uldbjerg N, Nielsen BB, Gravholt CH. Only a minority of sex chromosome abnormalities are detected by a national prenatal screening program for Down syndrome. Hum Reprod. 2015;30:2419–2426. doi: 10.1093/humrep/dev192. - DOI - PubMed
    1. Koeberl DD, McGillivray B, Sybert VP. Prenatal diagnosis of 45,X/46,XX mosaicism and 45,X: implications for postnatal outcome. Am J Hum Genet. 1995;57:661–666. - PMC - PubMed
    1. Murdock DR, Donovan FX, Chandrasekharappa SC, et al. Whole-exome sequencing for diagnosis of Turner syndrome: toward next-generation sequencing and newborn screening. J Clin Endocrinol Metab. 2017;102:1529–1537. doi: 10.1210/jc.2016-3414. - DOI - PMC - PubMed

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