Prevalence, diagnostic features, and medical outcomes of females with Turner syndrome with a trisomy X cell line (45,X/47,XXX): Results from the InsighTS Registry.
Trisomy X syndrome
Turner syndrome
mosaicism
phenotype
sex chromosome aneuploidy
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
17 Jul 2024
17 Jul 2024
Historique:
revised:
27
06
2024
received:
17
04
2024
accepted:
07
07
2024
medline:
17
7
2024
pubmed:
17
7
2024
entrez:
17
7
2024
Statut:
aheadofprint
Résumé
Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly more likely to have structural renal anomalies (18% vs. 3%; p = 0.03). They were twice as likely to have congenital heart disease (32% vs. 15%, p = 0.08) and less likely to experience spontaneous menarche (46% vs. 75% of those over age 10, p = 0.06), although not statistically significant. Congenital anomalies, hypertension, and hearing loss were primarily attributable to a higher proportion of 45,X cells, while preserved ovarian function was most associated with a higher proportion of 46,XX cells. In this large TS cohort, 45,X/47,XXX was more common than previously reported, individuals were phenotypically less affected than those with 45,X, but did have trends for several more TS-related diagnoses than individuals with 45,X/46,XX.
Identifiants
pubmed: 39016627
doi: 10.1002/ajmg.a.63819
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e63819Subventions
Organisme : Turner Syndrome Global Alliance
Organisme : Turner Syndrome Colorado
Organisme : NIDDK NIH HHS
ID : K23 DK134810
Pays : United States
Organisme : National Science Foundation
ID : 2129088
Organisme : Boettcher Foundation
Organisme : NIH/NCATS
ID : UM1TR004399
Informations de copyright
© 2024 Wiley Periodicals LLC.
Références
Alvarez‐Nava, F., & Lanes, R. (2018). Epigenetics in Turner syndrome. Clinical Epigenetics, 10, 45.
Alvarez‐Nava, F., & Soto‐Quintana, M. (2022). The hypothesis of the prolonged cell cycle in Turner syndrome. Journal of Developmental Biology, 10(2), 16.
Barrenas, M., Landin‐Wilhelmsen, K., & Hanson, C. (2000). Ear and hearing in relation to genotype and growth in Turner syndrome. Hearing Research, 144(1–2), 21–28.
Bernard, V., Donadille, B., Zenaty, D., Courtillot, C., Salenave, S., Brac de la Perrière, A., Albarel, F., Fèvre, A., Kerlan, V., Brue, T., Delemer, B., Borson‐Chazot, F., Carel, J. C., Chanson, P., Léger, J., Touraine, P., Christin‐Maitre, S., & CMERC Center for Rare Disease. (2016). Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome. Human Reproduction, 31(4), 782–788.
Blair, J., Tolmie, J., Hollman, A. S., & Donaldson, M. D. C. (2001). Phenotype, ovarian function, and growth in patients with 45,X/47,XXX Turner mosaicism: Implications for prenatal counseling and estrogen therapy at puberty. The Journal of Pediatrics, 139(5), 724–728.
Bryman, I., Sylvén, L., Berntorp, K., Innala, E., Bergström, I., Hanson, C., Oxholm, M., & Landin‐Wilhelmsen, K. (2011). Pregnancy rate and outcome in Swedish women with Turner syndrome. Fertility and Sterility, 95(8), 2507–2510.
Cameron‐Pimblett, A., La Rosa, C., King, T. F. J., Davies, M. C., & Conway, G. S. (2017). The Turner syndrome life course project: Karyotype‐phenotype analyses across the lifespan. Clinical Endocrinology, 87(5), 532–538.
Clement‐Jones, M., Schiller, S., Rao, E., Blaschke, R. J., Zuniga, A., Zeller, R., Robson, S. C., Binder, G., Glass, I., Strachan, T., Lindsay, S., & Rappold, G. A. (2000). The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Human Molecular Genetics, 9(5), 695–702.
Davis, S. M., Soares, K., Howell, S., Cree‐Green, M., Buyers, E., Johnson, J., & Tartaglia, N. R. (2020). Diminished ovarian reserve in girls and adolescents with Trisomy X syndrome. Reproductive Sciences, 27(11), 1985–1991.
Denes, A. M., Landin‐Wilhelmsen, K., Wettergren, Y., Bryman, I., & Hanson, C. (2015). The proportion of diploid 46,XX cells increases with time in women with Turner syndrome—A 10‐year follow‐up study. Genetic Testing and Molecular Biomarkers, 19(2), 82–87.
Dowlut‐McElroy, T., Davis, S., Howell, S., Gutmark‐Little, I., Bamba, V., Prakash, S., Patel, S., Fadoju, D., Vijayakanthi, N., Haag, M., Hennerich, D., Dugoff, L., & Shankar, R. K. (2022). Cell‐free DNA screening positive for monosomy X: Clinical evaluation and management of suspected maternal or fetal Turner syndrome. American Journal of Obstetrics and Gynecology, 227(6), 862–870.
El‐Mansoury, M., Barrenäs, M.‐L., Bryman, I., Hanson, C., Larsson, C., Wilhelmsen, L., & Landin‐Wilhelmsen, K. (2007). Chromosomal mosaicism mitigates stigmata and cardiovascular risk factors in Turner syndrome. Clinical Endocrinology, 66(5), 744–751.
Fukami, M., Seki, A., & Ogata, T. (2016). SHOX haploinsufficiency as a cause of syndromic and nonsyndromic short stature. Molecular Syndromology, 7(1), 3–11.
Gaowei Wang, X. L., Wang, M., Wang, J., Zhang, Z., Allegaert, K., Mei, D., Zhang, Y., Luo, S., Fang, Y., Li, D., Chen, Y., & Wei, H. (2024). Evaluating the relationship between the proportion of X‐chromosome deletions and clinical manifestations in children with turner syndrome. Frontiers in Endocrinology, 15, 1324160.
Gravholt, C. H., Andersen, N. H., Christin‐Maitre, S., Davis, S. M., Duijnhouwer, A., Gawlik, A., Maciel‐Guerra, A. T., Gutmark‐Little, I., Fleischer, K., Hong, D., Klein, K. O., Prakash, S. K., Shankar, R. K., Sandberg, D. E., Sas, T. C. J., Skakkebæk, A., Stochholm, K., van der Velden, J. A., The International Turner Syndrome Consensus Group, … Backeljauw, P. F. (2024). Clinical practice guidelines for the care of girls and women with Turner syndrome. European Journal of Endocrinology, 190(6), G53–G151.
Gunther, D. F., Eugster, E., Zagar, A. J., Bryant, C. G., Davenport, M. L., & Quigley, C. A. (2004). Ascertainment bias in Turner syndrome: New insights from girls who were diagnosed incidentally in prenatal life. Pediatrics, 114(3), 640–644.
Harris, P. A., Taylor, R., Minor, B. L., Elliott, V., Fernandez, M., O'Neal, L., McLeod, L., Delacqua, G., Delacqua, F., Kirby, J., Duda, S. N., & REDCap Consortium. (2019). The REDCap consortium: Building an international community of software platform partners. Journal of Biomedical Informatics, 95, 103208.
Harris, P. A., Taylor, R., Thielke, R., Payne, J., Gonzalez, N., & Conde, J. G. (2009). Research electronic data capture (REDCap)—A metadata‐driven methodology and workflow process for providing translational research informatics support. Journal of Biomedical Informatics, 42(2), 377–381.
Kanakatti Shankar, R., Carl, A., Law, J. R., Bamba, V., Brickman, W. J., Prakash, S. K., Dowlut McElroy, T., Howell, S., Gutmark Little, I., Klein, K. O., Pinnaro, C. T., Ranallo, K., Good, M., & Davis, S. M. (2023). Inspiring new science to guide healthcare in Turner syndrome: Rationale, design, and methods for the InsighTS registry. American Journal of Medical Genetics. Part A, 194, 311–319.
Levine, M. S., & Holland, A. J. (2018). The impact of mitotic errors on cell proliferation and tumorigenesis. Genes & Development, 32(9–10), 620–638.
Lim, H. H., Kil, H. R., & Koo, S. H. (2017). Incidence, puberty, and fertility in 45,X/47,XXX mosaicism: Report of a patient and a literature review. American Journal of Medical Genetics. Part A, 173(7), 1961–1964.
Loscalzo, M. L., van, P., Ho, V. B., Bakalov, V. K., Rosing, D. R., Malone, C. A., Dietz, H. C., & Bondy, C. A. (2005). Association between fetal lymphedema and congenital cardiovascular defects in Turner syndrome. Pediatrics, 115(3), 732–735.
Michaeli, T., Jurges, H., & Michaeli, D. T. (2023). FDA approval, clinical trial evidence, efficacy, epidemiology, and price for non‐orphan and ultra‐rare, rare, and common orphan cancer drug indications: Cross sectional analysis. BMJ, 381, e073242.
Mondal, S., Bhattacharjee, R., Chowdhury, S., & Mukhopadhyay, S. (2021). Heterogeneity of karyotypes in Turner syndrome. Indian Journal of Pediatrics, 88(2), 175.
Nazarenko, S. A., Timoshevsky, V. A., & Sukhanova, N. N. (1999). High frequency of tissue‐specific mosaicism in Turner syndrome patients. Clinical Genetics, 56(1), 59–65.
Paton, G. R., Silver, M. F., & Allison, A. C. (1974). Comparison of cell cycle time in normal and trisomic cells. Humangenetik, 23(3), 173–182.
R Core Team. (2022). R: A language and environment for statistical computing. R Foundation for Statistical Computing.
Stochholm, K., Juul, S., & Gravholt, C. H. (2010). Mortality and incidence in women with 47,XXX and variants. American Journal of Medical Genetics. Part A, 152A(2), 367–372.
Sybert, V. P. (2002). Phenotypic effects of mosaicism for a 47,XXX cell line in Turner syndrome. Journal of Medical Genetics, 39(3), 217–220.
Tang, R., Lin, L., Guo, Z., Hou, H., & Yu, Q. (2019). Ovarian reserve evaluation in a woman with 45,X/47,XXX mosaicism: A case report and a review of literature. Molecular Genetics & Genomic Medicine, 7(7), e00732.
Tartaglia, N. R., Howell, S., Sutherland, A., Wilson, R., & Wilson, L. (2010). A review of trisomy X (47,XXX). Orphanet Journal of Rare Diseases, 5, 8.
Taylor, T. H., Gitlin, S. A., Patrick, J. L., Crain, J. L., Wilson, J. M., & Griffin, D. K. (2014). The origin, mechanisms, incidence and clinical consequences of chromosomal mosaicism in humans. Human Reproduction Update, 20(4), 571–581.
Tokita, M. J., & Sybert, V. P. (2016). Postnatal outcomes of prenatally diagnosed 45,X/46,XX. American Journal of Medical Genetics, 170A(5), 1196–1201.
Wigby, K., D'Epagnier, C., Howell, S., Reicks, A., Wilson, R., Cordeiro, L., & Tartaglia, N. (2016). Expanding the phenotype of Triple X syndrome: A comparison of prenatal versus postnatal diagnosis. American Journal of Medical Genetics. Part A, 170(11), 2870–2881.