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Tytuł:
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Artificial intelligence-assisted phenotype discovery of fragile X syndrome in a population-based sample.
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Autorzy:
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Movaghar A; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Page D; Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
Scholze D; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Hong J; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
DaWalt LS; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Kuusisto F; Morgridge Institute for Research, Madison, WI, USA.
Stewart R; Morgridge Institute for Research, Madison, WI, USA.
Brilliant M; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.; Marshfield Clinic Research Institute, Marshfield, WI, USA.
Mailick M; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA. .
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Źródło:
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Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2021 Jul; Vol. 23 (7), pp. 1273-1280. Date of Electronic Publication: 2021 Mar 26.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: 2022- : [New York] : Elsevier
Original Publication: Baltimore, MD : Lippincott, Williams & Wilkins, c1998-
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MeSH Terms:
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Fragile X Syndrome*/diagnosis
Fragile X Syndrome*/epidemiology
Fragile X Syndrome*/genetics
Intellectual Disability*/diagnosis
Intellectual Disability*/epidemiology
Intellectual Disability*/genetics
Artificial Intelligence ; Humans ; Machine Learning ; Phenotype
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References:
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Warren, S. T. The epigenetics of fragile X syndrome. Cell Stem Cell. 1, 488–489 (2007). (PMID: 10.1016/j.stem.2007.10.017)
Bailey, D. B., Skinner, D. & Sparkman, K. L. Discovering fragile X syndrome: family experiences and perceptions. Pedatrics. 111, 407–416 (2003). (PMID: 10.1542/peds.111.2.407)
Hagerman, R. J. et al. Fragile X syndrome. Nat. Rev. Dis. Primers. 3, 17065 (2017).
Bagni, C., Tassone, F., Neri, G. & Hagerman, R. Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics. J. Clin. Invest. 122, 4314–4322 (2012). (PMID: 10.1172/JCI63141)
Abrams, L. et al. Newborn, carrier, and early childhood screening recommendations for fragile X. Pediatrics. 130, 1126–1135 (2012). (PMID: 10.1542/peds.2012-0693)
Bailey, D. B., Raspa, M., Bishop, E. & Holiday, D. No change in the age of diagnosis for fragile X syndrome: findings from a national parent survey. Pediatrics. 124, 527–533 (2009). (PMID: 10.1542/peds.2008-2992)
Visootsak, J. et al. Importance of a specialty clinic for individuals with fragile X syndrome. Am. J. Med. Genet. A. 170, 3144–3149 (2016). (PMID: 10.1002/ajmg.a.37982)
Raspa, M., Wheeler, A. C. & Riley, C. Public health literature review of fragile X syndrome. Pediatrics. 139, S153–S171 (2017). (PMID: 10.1542/peds.2016-1159C)
Gabis, L. V. et al. Prolonged time lag to final diagnosis of fragile X syndrome. J Pediatr. 193, 217–221.e1 (2018). (PMID: 10.1016/j.jpeds.2017.10.008)
Salcedo-Arellano, M. J., Dufour, B., McLennan, Y., Martinez-Cerdeno, V. & Hagerman, R. Fragile X syndrome and associated disorders: clinical aspects and pathology. Neurobiol. Dis. 136, 104740 (2020). (PMID: 10.1016/j.nbd.2020.104740)
Johnson, K., Herring, J. & Richstein, J. Fragile X Premutation Associated Conditions (FXPAC). Front. Pediatr. 8, 266 (2020).
Movaghar, A. et al. Data-driven phenotype discovery of FMR1 premutation carriers in a population-based sample. Sci. Adv. 5, eaaw7195 (2019). (PMID: 10.1126/sciadv.aaw7195)
Nolin, S. L. et al. Expansions and contractions of the FMR1 CGG repeat in 5,508 transmissions of normal, intermediate, and premutation alleles. Am. J. Med. Genet. A. 179, 1148–1156 (2019). (PMID: 10.1002/ajmg.a.61165)
Wotton, T. et al. Are we ready for fragile X newborn screening testing?—lessons learnt from a feasibility study. Int. J. Neonatal Screen. 4, 9 (2018). (PMID: 10.3390/ijns4010009)
Bailey, D. B. Early intervention and newborn screening: parallel roads or divergent highways? Infants Young Child. 34, 3–16 (2021). (PMID: 10.1097/IYC.0000000000000181)
Kidd, S. A. et al. Fragile X syndrome: a review of associated medical problems. Pediatrics. 134, 995–1005 (2014). (PMID: 10.1542/peds.2013-4301)
Utari, A. et al. Aging in fragile X syndrome. J. Neurodev. Disord. 2, 70–76 (2010). (PMID: 10.1007/s11689-010-9047-2)
Bailey, D. B., Raspa, M., Olmsted, M. & Holiday, D. B. Co-occurring conditions associated with FMR1 gene variations: findings from a national parent survey. Am. J. Med. Genet. A. 146A, 2060–2069 (2008). (PMID: 10.1002/ajmg.a.32439)
Cordeiro, L., Ballinger, E., Hagerman, R. & Hessl, D. Clinical assessment of DSM-IV anxiety disorders in fragile X syndrome: prevalence and characterization. J. Neurodev. Disord. 3, 57–67 (2011). (PMID: 10.1007/s11689-010-9067-y)
Visootsak, J., Warren, S. T., Anido, A. & Graham, J. M. Fragile X syndrome: an update and review for the primary pediatrician. Clin. Pediatr. (Phila). 44, 371–381 (2005). (PMID: 10.1177/000992280504400501)
Greenberg, J. S. et al. Family environment and behavior problems in children, adolescents, and adults with fragile X syndrome. Am. J. Intellect. Dev. Disabil. 117, 331–346 (2012). (PMID: 10.1352/1944-7558-117.4.331)
Sullivan, K. et al. ADHD symptoms in children with FXS. Am. J. Med. Genet. A. 140A, 2275–2288 (2006). (PMID: 10.1002/ajmg.a.31388)
Kronk, R. et al. Prevalence, nature, and correlates of sleep problems among children with fragile X syndrome based on a large scale parent survey. Sleep. 33, 679–687 (2010). (PMID: 10.1093/sleep/33.5.679)
Finestack, L. H., Richmond, E. K. & Abbeduto, L. Language development in individuals with fragile X syndrome. Top. Lang. Disord. 29, 133–148 (2009). (PMID: 10.1097/TLD.0b013e3181a72016)
Baranek, G. T. et al. Developmental trajectories and correlates of sensory processing in young boys with fragile X syndrome. Phys. Occup. Ther. Pediatr. 28, 79–98 (2008). (PMID: 10.1300/J006v28n01_06)
Berry-Kravis, E. et al. Seizures in fragile X syndrome: characteristics and comorbid diagnoses. Am. J. Intellect. Dev. Disabil. 115, 461–472 (2010). (PMID: 10.1352/1944-7558-115.6.461)
Sherman, S. L. et al. FORWARD: a registry and longitudinal clinical database to study fragile X syndrome. Pediatrics. 139, S183–S193 (2017). (PMID: 10.1542/peds.2016-1159E)
Kohane, I. S. Using electronic health records to drive discovery in disease genomics. Nat. Rev. Genet. 12, 417–428 (2011). (PMID: 10.1038/nrg2999)
Israel, R. A. The International Classification of Disease. Two hundred years of development. Public Health Rep. 93, 150 (1978). (PMID: 6350891431884)
Rasmussen, L. V. et al. Design patterns for the development of electronic health record-driven phenotype extraction algorithms. J. Biomed. Inform. 51, 280–286 (2014). (PMID: 10.1016/j.jbi.2014.06.007)
Breiman, L. Random forests. Mach. Learn. 45, 5–32 (2001). (PMID: 10.1023/A:1010933404324)
Denny, J. C. et al. Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data. Nat. Biotechnol. 31, 1102–1111 (2013). (PMID: 10.1038/nbt.2749)
Rousseau, F. et al. Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. N. Engl. J. Med. 325, 1673–1681 (1991). (PMID: 10.1056/NEJM199112123252401)
Laxman, D. J. et al. Medication use by adolescents and adults with fragile X syndrome: medication use by individuals with FXS. J. Intellect. Disabil. Res. 62, 94–105 (2018). (PMID: 10.1111/jir.12433)
Riggs J. E. Neurologic Complications of Electrolyte Disturbances. In: Aminoff’s Neurology and General Medicine. Elsevier/Academic Press; Amsterdam; 2014:317–326. https://doi.org/10.1016/B978-0-12-407710-2.00017-5 .
Ridaura-Ruiz, L., Quinteros-Borgarello, M., Berini-Aytés, L. & Gay-Escoda C. Fragile X-syndrome: literature review and report of two cases. Med. Oral Patol. Oral Cir. Bucal. 14, e434-9 (2009).
Kaufmann, W. E. et al. Autism spectrum disorder in fragile X syndrome: cooccurring conditions and current treatment. Pediatrics. 139, S194–S206 (2017). (PMID: 10.1542/peds.2016-1159F)
Hyman, S. L., Levy, S. E., Myers, S. M. & Council On Children With Disabilities, Section on Developmental and Behavioral Pediatrics. Identification, evaluation, and management of children with autism spectrum disorder. Pediatrics. 145, e20193447 (2020).
Filipek, P. A. et al. Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society. Neurology. 55, 468–479 (2000). (PMID: 10.1212/WNL.55.4.468)
Greenlee, R. T. Measuring disease frequency in the Marshfield Epidemiologic Study Area (MESA). Clin. Med. Res. 1, 273–280 (2003). (PMID: 10.3121/cmr.1.4.273)
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Grant Information:
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UL1 TR000427 United States TR NCATS NIH HHS; R01 HD082110 United States HD NICHD NIH HHS; UL1 TR002373 United States TR NCATS NIH HHS; U54 HD090256 United States HD NICHD NIH HHS; U01 HG008701 United States HG NHGRI NIH HHS
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Entry Date(s):
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Date Created: 20210327 Date Completed: 20210812 Latest Revision: 20221115
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Update Code:
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20240105
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PubMed Central ID:
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PMC8257481
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DOI:
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10.1038/s41436-021-01144-7
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PMID:
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33772223
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Purpose: Fragile X syndrome (FXS), the most prevalent inherited cause of intellectual disability, remains underdiagnosed in the general population. Clinical studies have shown that individuals with FXS have a complex health profile leading to unique clinical needs. However, the full impact of this X-linked disorder on the health of affected individuals is unclear and the prevalence of co-occurring conditions is unknown.
Methods: We mined the longitudinal electronic health records from more than one million individuals to investigate the health characteristics of patients who have been clinically diagnosed with FXS. Additionally, using machine-learning approaches, we created predictive models to identify individuals with FXS in the general population.
Results: Our discovery-oriented approach identified the associations of FXS with a wide range of medical conditions including circulatory, endocrine, digestive, and genitourinary, in addition to mental and neurological disorders. We successfully created predictive models to identify cases five years prior to clinical diagnosis of FXS without relying on any genetic or familial data.
Conclusion: Although FXS is often thought of primarily as a neurological disorder, it is in fact a multisystem syndrome involving many co-occurring conditions, some primary and some secondary, and they are associated with a considerable burden on patients and their families.
Comment in: Genet Med. 2022 Mar;24(3):752-753. (PMID: 34906516)
Comment in: Genet Med. 2022 Mar;24(3):749-751. (PMID: 34906522)