Amniotic fluid RNA gene expression profiling provides insights into the phenotype of Turner syndrome
Open accessAbstract
Turner syndrome is a sex chromosome aneuploidy with characteristic malformations. Amniotic fluid, a complex biological material, could contribute to the understanding of Turner syndrome pathogenesis. In this pilot study, global gene expression analysis of cell-free RNA in amniotic fluid supernatant was utilized to identify specific genes/organ systems that may play a role in Turner syndrome pathophysiology. Cell-free RNA from amniotic fluid of five mid-trimester Turner syndrome fetuses and five euploid female fetuses matched for gestational age was extracted, amplified, and hybridized onto Affymetrix(®) U133 Plus 2.0 arrays. Significantly differentially regulated genes were identified using paired t tests. Biological interpretation was performed using Ingenuity Pathway Analysis and BioGPS gene expression atlas. There were 470 statistically significantly differentially expressed genes identified. They were widely distributed across the genome. XIST was significantly down-regulated (p < 0.0001); SHOX was not differentially expressed. One of the most highly represented organ systems was the hematologic/immune system, distinguishing the Turner syndrome transcriptome from other aneuploidies we previously studied. Manual curation of the differentially expressed gene list identified genes of possible pathologic significance, including NFATC3, IGFBP5, and LDLR. Transcriptomic differences in the amniotic fluid of Turner syndrome fetuses are due to genome-wide dysregulation. The hematologic/immune system differences may play a role in early-onset autoimmune dysfunction. Other genes identified with possible pathologic significance are associated with cardiac and skeletal systems, which are known to be affected in females with Turner syndrome. The discovery-driven approach described here may be useful in elucidating novel mechanisms of disease in Turner syndrome.
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There is evidence of a unique and tissue-specific genome-wide methylation and transcription landscape in TS extending to both the X chromosome and the autosomes.
“There is evidence of a unique and tissue-specific genome-wide methylation and transcription landscape in TS extending to both the X chromosome and the autosomes.103-109”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [109]
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Cites
Calcium's Role in Mechanotransduction during Muscle Development
Damm, T. B., & Egli, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356667 · Cited by 14,548 · see citing works
Minimum information about a microarray experiment (MIAME)-toward standards for microarray data
Brazma, A., Hingamp, P., Quackenbush, J., Sherlock, G., Spellman, P., Stoeckert, C., Aach, J., Ansorge, W., Ball, C. A., Causton, H. C., et al. (2001) · Nature Genetics · doi:10.1038/ng1201-365 · Cited by 4,109 · see citing works
A gene atlas of the mouse and human protein-encoding transcriptomes
Su, A. I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K. A., Block, D., Zhang, J., Soden, R., Hayakawa, M., Kreiman, G., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400782101 · Cited by 3,475 · see citing works
BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources
Wu, C., Orozco, C., Boyer, J., Leglise, M., Goodale, J., Batalov, S., Hodge, C. L., Haase, J., Janes, J. O., Huss, J. W., et al. (2009) · Genome biology · doi:10.1186/gb-2009-10-11-r130 · Cited by 1,374 · see citing works
Nielsen, J., & Wohlert, M. (1991) · Human Genetics · doi:10.1007/bf01213097 · Cited by 1,193 · see citing works
Care of girls and women with Turner syndrome: a guideline of the Turner syndrome study group
Bondy, C. A. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1374 · Cited by 1,005 · see citing works
Sybert, V. P., & McCauley, E. (2004) · New England Journal of Medicine · doi:10.1056/nejmra030360 · Cited by 918 · see citing works
Gravholt, C. H., Juul, S., Naeraa, R. W., & Hansen, J. (1998) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(97)00237-0 · Cited by 548 · cited 1× · see citing works
“Hyperlipidemia and atherosclerosis are well known to be associated with turner syndrome (ross et al. 1995; elsheikh et al. 2002; Bondy 2007; Giordano et al. 2011; Gravholt et al. 1998). the risk of hypertension is increased threefold in individuals with turner syndrome (Gravholt et al. 1998).”
Turner's Syndrome in Adulthood
Elsheikh, M., Dunger, D. B., Conway, G. S., & Wass, J. A. H. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.1.0457 · Cited by 397 · see citing works
Horsley, V., & Pavlath, G. K. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200111073 · Cited by 319 · see citing works
Epidemiological, endocrine and metabolic features in Turner syndrome
Gravholt, C. H. (2004) · European Journal of Endocrinology · doi:10.1530/eje.0.1510657 · Cited by 248 · see citing works
Clarkson, P. M., Nicholson, M. R., Barratt‐Boyes, B. G., et al. (1983) · The American Journal of Cardiology · doi:10.1016/0002-9149(83)90661-6 · Cited by 244 · see citing works
Fetology: Diagnosis and Management of the Fetal Patient
Bianchi, D. W. (2000) · Cited by 229 · see citing works
Self-citationKim, K. S., Seu, Y. B., Baek, S.-H., Kim, M. J., Kim, K. J., Kim, J. H., & Kim, J.-R. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-03-0280 · Cited by 199 · see citing works
Salih, D. A. M., Tripathi, G., Holding, C., Szestak, T., Gonzalez, M. I., Carter, E. J., Cobb, L. J., Eisemann, J. H., & Pell, J. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400230101 · Cited by 184 · see citing works
Autoimmune diseases in women with Turner's Syndrome
Jørgensen, K. T., Rostgaard, K., Bache, I., Biggar, R. J., Nielsen, N. M., Tommerup, N., & Frisch, M. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27270 · Cited by 176 · see citing works
The effect of replication on gene expression microarray experiments
Pavlidis, P., Li, Q., & Noble, W. S. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btg227 · Cited by 150 · see citing works
Bakalov, V. K., Gutin, L. S., Cheng, C. M., Zhou, J., Sheth, P., Shah, K. R., Arepalli, S., Vanderhoof, V. H., Nelson, L. M., & Bondy, C. A. (2012) · Journal of Autoimmunity · doi:10.1016/j.jaut.2012.01.015 · Cited by 140 · see citing works
Slonim, D. K., Koide, K., Johnson, K. L., Tantravahi, U., Cowan, J. M., Jarrah, Z., & Bianchi, D. W. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903909106 · Cited by 117 · see citing works
Self-citationThe STAT3-IGFBP5 axis is critical for IL-6/gp130-induced premature senescence in human fibroblasts
Kojima, H., Kunimoto, H., Inoue, T., & Nakajima, K. (2012) · Cell Cycle · doi:10.4161/cc.11.4.19172 · Cited by 114 · see citing works
Fetology. Diagnosis and Management of the Fetal Patient
Leonte, L. D. (2013) · Acta Endocrinologica (Bucharest) · doi:10.4183/aeb.2013.657 · Cited by 108 · see citing works
Lipid abnormalities in Turner syndrome
ROSS, J. L., Feuillan, P., Long, L., Kowal, K., Kushner, H., & Cutler, G. B. (1995) · The Journal of Pediatrics · doi:10.1016/s0022-3476(95)70551-1 · Cited by 101 · see citing works
Devlin, R. D., Du, Z., Buccilli, V., Jorgetti, V., & CANALIS, E. M. (2002) · Endocrinology · doi:10.1210/en.2002-220129 · Cited by 95 · see citing works
Monosomy for the X-Chromosome Is Associated with an Atherogenic Lipid Profile
Van, P. L., Bakalov, V. K., & Bondy, C. A. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0503 · Cited by 89 · see citing works
Kenny, D. P., Polson, J. W., Martin, R. P., et al. (2011) · Hypertension Research · doi:10.1038/hr.2011.22 · Cited by 78 · see citing works
Prenatal Diagnosis of Turner Syndrome: Report on 69 Cases
Papp, C., Beke, A., Mezei, G., Szigeti, Z., Bán, Z., & Papp, Z. (2006) · Journal of Ultrasound in Medicine · doi:10.7863/jum.2006.25.6.711 · Cited by 74 · see citing works
NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice
Bierer, R., Nitta, C. H., Friedman, J. K., et al. (2011) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00405.2010 · Cited by 71 · see citing works
Larrabee, P. B. (2005) · JAMA · doi:10.1001/jama.293.7.836 · Cited by 68 · see citing works
The Amniotic Fluid Transcriptome
Hui, L., Slonim, D. K., Wick, H. C., Johnson, K. L., & Bianchi, D. W. (2011) · Obstetrics and Gynecology · doi:10.1097/aog.0b013e31823d4150 · Cited by 57 · see citing works
Self-citationGiordano, R., Forno, D., Lanfranco, F., Manieri, C., Ghizzoni, L., & Ghigo, E. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0002 · Cited by 56 · see citing works
Transcriptomic analysis of cell-free fetal RNA suggests a specific molecular phenotype in trisomy 18
Koide, K., Slonim, D. K., Johnson, K. L., Tantravahi, U., Cowan, J. M., & Bianchi, D. W. (2010) · Human Genetics · doi:10.1007/s00439-010-0923-3 · Cited by 53 · see citing works
Self-citationKanatani, M., Sugimoto, T., Nishiyama, K., & Chihara, K. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.5.902 · Cited by 49 · see citing works
Maternal-Fetal Immune Tolerance, Block by Block
Gobert, M., & Lafaille, J. J. (2012) · Cell · doi:10.1016/j.cell.2012.06.020 · Cited by 36 · see citing works
Growth parameters in mid-trimester fetal Turner syndrome
Fitzsimmons, J., Fantel, A. G., & Shepard, T. H. (1994) · Early Human Development · doi:10.1016/0378-3782(94)90223-2 · Cited by 36 · see citing works
Down syndrome, Turner syndrome, and Klinefelter syndrome: primary care throughout the life span
Tyler, C. V., & Edman, J. C. (2004) · Primary Care Clinics in Office Practice · doi:10.1016/j.pop.2004.04.006 · Cited by 33 · see citing works
NFATc3 contributes to intermittent hypoxia-induced arterial remodeling in mice
de Frutos, S., Caldwell, E., Nitta, C. H., et al. (2010) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00341.2010 · Cited by 31 · see citing works
Hui, L., Slonim, D. K., Wick, H. C., et al. (2012) · Human Genetics · doi:10.1007/s00439-012-1195-x · Cited by 30 · see citing works
Self-citationDietz, J. A., Johnson, K. L., Massingham, L. J., et al. (2011) · Prenatal Diagnosis · doi:10.1002/pd.2732 · Cited by 13 · see citing works
Self-citationHintz, R. L. (2002) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/a:1020909925921 · Cited by 11 · see citing works
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Clinical practice guidelines for the care of girls and women with Turner syndrome.
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., et al. (2024) · European Journal of Endocrinology · doi:10.1093/ejendo/lvae050 · Cited by 224 · see citing works
Widespread DNA hypomethylation and differential gene expression in Turner syndrome
Trolle, C., Nielsen, M. M., Skakkebæk, A., Lamy, P., Vang, S., Hedegaard, J., Nordentoft, I., Ørntoft, T. F., Pedersen, J. S., & Gravholt, C. H. (2016) · Scientific Reports · doi:10.1038/srep34220 · Cited by 149 · see citing works
Zhang, X., Hong, D., Ma, S., Ward, T., Ho, M., Pattni, R., Duren, Z., Stankov, A., Bade Shrestha, S., Hallmayer, J., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1910003117 · Cited by 101 · see citing works
Sharma, A., Jamil, M. A., Nuesgen, N., Schreiner, F., Priebe, L., Hoffmann, P., Herns, S., Nöthen, M. M., Fröhlich, H., Oldenburg, J., et al. (2015) · Clinical Epigenetics · doi:10.1186/s13148-015-0112-2 · Cited by 81 · see citing works
Epigenetics in Turner syndrome
Álvarez-Nava, F., & Lanes, R. (2018) · Clinical Epigenetics · doi:10.1186/s13148-018-0477-0 · Cited by 79 · see citing works
- Authors
- Massingham, L. J., Johnson, K. L., Scholl, T. M., Slonim, D. K., Wick, H. C., & Bianchi, D. W.
- Affiliations
- Tufts Medical Center (US)
- Tufts University (US)
- LabCorp (United States) (US)
- Corresponding author
- Massingham, Lauren J.
- Venue
- Human Genetics
- Published
- 2014-05-22
- Volume
- 133
- Issue
- 9
- Pages
- 1075-1082
- ISSN
- 0018-7348 (ISSN-L)
- 0340-6717
- 1432-1203
- PMC
- PMC4384642
- OpenAlex
- W2092774579
- Cited by
- 52
- References
- 39
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 6 · 2014: 1
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD058880, R01HD042053, R01HD42053-10)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Turner syndrome, amniotic fluid, cell-free RNA, gene expression profiling, sex chromosome aneuploidy, XIST, SHOX, autoimmune dysfunction, NFATc3, IGFBP-5, LDL receptor
- MeSH terms
- Amniotic Fluid, Aneuploidy, Female, Humans, Organ Specificity, Phenotype, Pilot Projects, Pregnancy, RNA, Messenger, Turner Syndrome, Down-Regulation, Up-Regulation, Case-Control Studies, DNA, Complementary, Gene Expression Regulation, Developmental, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Chromosomes, Human, X, Transcriptome, Karyotype
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