{"PubmedArticle":{"MedlineCitation":{"@attributes":{"Status":"MEDLINE","Owner":"NLM","IndexingMethod":"Automated"},"PMID":{"@attributes":{"Version":"1"},"@text":"37312416"},"DateCompleted":{"Year":"2023","Month":"06","Day":"29"},"DateRevised":{"Year":"2025","Month":"06","Day":"26"},"Article":{"@attributes":{"PubModel":"Print"},"Journal":{"ISSN":{"@attributes":{"IssnType":"Electronic"},"@text":"1365-2990"},"JournalIssue":{"@attributes":{"CitedMedium":"Internet"},"Volume":"49","Issue":"3","PubDate":{"Year":"2023","Month":"Jun"}},"Title":"Neuropathology and applied neurobiology","ISOAbbreviation":"Neuropathol Appl Neurobiol"},"ArticleTitle":"Intelligence quotient-genotype association in dystrophinopathies: A systematic review and meta-analysis.","Pagination":{"StartPage":"e12914","MedlinePgn":"e12914"},"ELocationID":[{"@attributes":{"EIdType":"doi","ValidYN":"Y"},"@text":"10.1111\/nan.12914"}],"Abstract":{"AbstractText":[{"@attributes":{"Label":"AIMS"},"@text":"Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD) are associated with intelligence quotients (IQs) lower than the normative values, and it is suggested that IQ is negatively correlated with the number of affected isoforms (i.e., Dp427, Dp140 and Dp71). Therefore, the objective of this meta-analysis was to estimate the IQ, and the IQ-genotype association according to the altered dystrophin isoforms, in the population with BMD or DMD."},{"@attributes":{"Label":"METHODS"},"@text":"A systematic search in Medline, Web of Science, Scopus and the Cochrane Library was conducted from inception to March 2023. Observational studies that determined the IQ and\/or the IQ by genotype in the population with BMD or DMD were included. Meta-analyses of IQ, IQ by genotype and IQ-genotype association by comparing IQ according to the genotype were conducted. The results are shown as the mean\/mean differences and 95% confidence intervals."},{"@attributes":{"Label":"RESULTS"},"@text":"Fifty-one studies were included. The IQ in BMD was 89.92 (85.84, 94.01) and in DMD was 84.61 (82.97, 86.26). Moreover, the IQ for Dp427-\/Dp140+\/Dp71+ and Dp427-\/Dp140-\/Dp71+ was 90.62 (86.72, 94.53) and 80.73 (67.49, 93.98) in BMD, while the IQ for Dp427-\/Dp140+\/Dp71+, Dp427-\/Dp140-\/Dp71+ and Dp427-\/Dp140-\/Dp71- was 93.05 (89.42, 96.67), 81.78 (77.23, 86.32) and 49.19 (40.47, 57.90) in DMD. Finally, in DMD, Dp427-\/Dp140-\/Dp71+ vs Dp427-\/Dp140+\/Dp71+ and Dp427-\/Dp140-\/Dp71- vs Dp427-\/Dp140-\/Dp71+ were associated with -10.73 (-14.66, -6.81) and -36.14 (-48.87, -23.41) points, respectively."},{"@attributes":{"Label":"CONCLUSIONS"},"@text":"The IQ in BMD and DMD was lower than the normative values. Moreover, in DMD, there is a synergistic association between the number of affected isoforms and IQ."}],"CopyrightInformation":"\u00a9 2023 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society."},"AuthorList":{"@attributes":{"CompleteYN":"Y"},"Author":[{"@attributes":{"ValidYN":"Y"},"LastName":"Pascual-Morena","ForeName":"Carlos","Initials":"C","AffiliationInfo":[{"Affiliation":"Health and Social Research Center, Universidad de Castilla-La Mancha, Cuenca, Spain."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Cavero-Redondo","ForeName":"Iv\u00e1n","Initials":"I","AffiliationInfo":[{"Affiliation":"Facultad de Ciencias de la Salud, Universidad Aut\u00f3noma de Chile, Talca, Chile."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Sequ\u00ed-Dom\u00ednguez","ForeName":"Irene","Initials":"I","AffiliationInfo":[{"Affiliation":"Health and Social Research Center, Universidad de Castilla-La Mancha, Cuenca, Spain."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Rodr\u00edguez-Guti\u00e9rrez","ForeName":"Eva","Initials":"E","AffiliationInfo":[{"Affiliation":"Health and Social Research Center, Universidad de Castilla-La Mancha, Cuenca, Spain."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Visier-Alfonso","ForeName":"Mar\u00eda Eugenia","Initials":"ME","AffiliationInfo":[{"Affiliation":"Health and Social Research Center, Universidad de Castilla-La Mancha, Cuenca, Spain."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Mart\u00ednez-Vizca\u00edno","ForeName":"Vicente","Initials":"V","Identifier":[{"@attributes":{"Source":"ORCID"},"@text":"0000-0001-6121-7893"}],"AffiliationInfo":[{"Affiliation":"Health and Social Research Center, Universidad de Castilla-La Mancha, Cuenca, Spain."},{"Affiliation":"Facultad de Ciencias de la Salud, Universidad Aut\u00f3noma de Chile, Talca, Chile."}]}]},"Language":["eng"],"PublicationTypeList":{"PublicationType":[{"@attributes":{"UI":"D017418"},"@text":"Meta-Analysis"},{"@attributes":{"UI":"D000078182"},"@text":"Systematic Review"},{"@attributes":{"UI":"D016428"},"@text":"Journal Article"},{"@attributes":{"UI":"D013485"},"@text":"Research Support, Non-U.S. Gov't"}]}},"MedlineJournalInfo":{"Country":"England","MedlineTA":"Neuropathol Appl Neurobiol","NlmUniqueID":"7609829","ISSNLinking":"0305-1846"},"ChemicalList":{"Chemical":[{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D016189"},"@text":"Dystrophin"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D020033"},"@text":"Protein Isoforms"}}]},"CitationSubset":["IM"],"MeshHeadingList":{"MeshHeading":[{"DescriptorName":{"@attributes":{"UI":"D006801","MajorTopicYN":"N"},"@text":"Humans"}},{"DescriptorName":{"@attributes":{"UI":"D016189","MajorTopicYN":"Y"},"@text":"Dystrophin"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"N"},"@text":"genetics"}]},{"DescriptorName":{"@attributes":{"UI":"D020388","MajorTopicYN":"Y"},"@text":"Muscular Dystrophy, Duchenne"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"N"},"@text":"genetics"}]},{"DescriptorName":{"@attributes":{"UI":"D020033","MajorTopicYN":"N"},"@text":"Protein Isoforms"}},{"DescriptorName":{"@attributes":{"UI":"D007360","MajorTopicYN":"N"},"@text":"Intelligence"},"QualifierName":[{"@attributes":{"UI":"Q000235","MajorTopicYN":"N"},"@text":"genetics"}]}]},"KeywordList":[{"@attributes":{"Owner":"NOTNLM"},"Keyword":[{"@attributes":{"MajorTopicYN":"N"},"@text":"cognition"},{"@attributes":{"MajorTopicYN":"N"},"@text":"muscular dystrophy"},{"@attributes":{"MajorTopicYN":"N"},"@text":"muscular dystrophy, Duchenne"},{"@attributes":{"MajorTopicYN":"N"},"@text":"neuromuscular diseases"},{"@attributes":{"MajorTopicYN":"N"},"@text":"review"}]}]},"PubmedData":{"History":{"PubMedPubDate":[{"@attributes":{"PubStatus":"revised"},"Year":"2023","Month":"4","Day":"3"},{"@attributes":{"PubStatus":"received"},"Year":"2022","Month":"11","Day":"23"},{"@attributes":{"PubStatus":"accepted"},"Year":"2023","Month":"6","Day":"3"},{"@attributes":{"PubStatus":"medline"},"Year":"2023","Month":"6","Day":"29","Hour":"6","Minute":"43"},{"@attributes":{"PubStatus":"pubmed"},"Year":"2023","Month":"6","Day":"14","Hour":"6","Minute":"42"},{"@attributes":{"PubStatus":"entrez"},"Year":"2023","Month":"6","Day":"14","Hour":"1","Minute":"22"}]},"PublicationStatus":"ppublish","ArticleIdList":{"ArticleId":[{"@attributes":{"IdType":"pubmed"},"@text":"37312416"},{"@attributes":{"IdType":"doi"},"@text":"10.1111\/nan.12914"}]},"ReferenceList":[{"Title":"REFERENCES","Reference":[{"Citation":"Holland A, Carberry S, Ohlendieck K. Proteomics of the dystrophin-glycoprotein complex and dystrophinopathy. Curr Protein Pept Sci. 2013;14(8):680-697. doi:10.2174\/13892037113146660083"},{"Citation":"Waldrop MA, Flanigan KM. Update in Duchenne and Becker muscular dystrophy. Curr Opin Neurol. 2019;32(5):722-727. doi:10.1097\/WCO.0000000000000739"},{"Citation":"Bushby KM, Thambyayah M, Gardner-Medwin D. Prevalence and incidence of Becker muscular dystrophy. Lancet (London, England). 1991;337(8748):1022-1024. doi:10.1016\/0140-6736(91)92671-n"},{"Citation":"Mah JK, Korngut L, Dykeman J, Day L, Pringsheim T, Jette N. A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 2014;24(6):482-491. doi:10.1016\/j.nmd.2014.03.008"},{"Citation":"Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018;17(3):251-267. doi:10.1016\/S1474-4422(18)30024-3"},{"Citation":"Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 2018;17(4):347-361. doi:10.1016\/S1474-4422(18)30025-5"},{"Citation":"Pascual-Morena C, Cavero-Redondo I, \u00c1lvarez-Bueno C, Mesas AE, Pozuelo-Carrascosa D, Mart\u00ednez-Vizca\u00edno V. Restorative treatments of dystrophin expression in Duchenne muscular dystrophy: a systematic review. Ann Clin Transl Neurol. 2020;7(9):1738-1752. doi:10.1002\/acn3.51149"},{"Citation":"Goemans N. How glucocorticoids change life in Duchenne muscular dystrophy. Lancet. 2018;391(10119):406-407. doi:10.1016\/S0140-6736(17)32405-4"},{"Citation":"Pascual-Morena C, Cavero-Redondo I, Saz-Lara A, Sequ\u00ed-Dom\u00ednguez I, Lucer\u00f3n-Lucas-Torres M, Mart\u00ednez-Vizca\u00edno V. Genetic modifiers and phenotype of Duchenne muscular dystrophy: a systematic review and meta-analysis. Pharmaceuticals (Basel). 2021;14(8):798. doi:10.3390\/PH14080798"},{"Citation":"Ricotti V, Roberts RG, Muntoni F. Dystrophin and the brain. Dev Med Child Neurol. 2011;53(1):12. doi:10.1111\/j.1469-8749.2010.03836.x"},{"Citation":"Ferrero A, Rossi M. Cognitive profile and neuropsychiatric disorders in Becker muscular dystrophy: a systematic review of literature. Neurosci Biobehav Rev. 2022;137:104648. doi:10.1016\/j.neubiorev.2022.104648"},{"Citation":"Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan. Lancet Neurol. 2018;17(5):445-455. doi:10.1016\/S1474-4422(18)30026-7"},{"Citation":"Doorenweerd N. Combining genetics, neuropsychology and neuroimaging to improve understanding of brain involvement in Duchenne muscular dystrophy-a narrative review. Neuromuscul Disord. 2020;30(6):437-442. doi:10.1016\/j.nmd.2020.05.001"},{"Citation":"Naidoo M, Anthony K. Dystrophin Dp71 and the neuropathophysiology of Duchenne muscular dystrophy. Mol Neurobiol. 2020;57(3):1748-1767. doi:10.1007\/s12035-019-01845-w"},{"Citation":"Daoud F, Candelario-Mart\u00ednez A, Billard J-M, et al. Role of mental retardation-associated dystrophin-gene product Dp71 in excitatory synapse organization, synaptic plasticity and behavioral functions. PLoS ONE. 2009;4(8):e6574. doi:10.1371\/journal.pone.0006574"},{"Citation":"Cotton S, Voudouris NJ, Greenwood KM. Intelligence and Duchenne muscular dystrophy: full-scale, verbal, and performance intelligence quotients. Dev Med Child Neurol. 2001;43(07):497-501. doi:10.1017\/S0012162201000913"},{"Citation":"Cotton SM, Voudouris NJ, Greenwood KM. Association between intellectual functioning and age in children and young adults with Duchenne muscular dystrophy: further results from a meta-analysis. Dev Med Child Neurol. 1999;47(4):257-265. doi:10.1017\/s0012162205000496"},{"Citation":"Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series. John Wiley and Sons; 2008. doi:10.1002\/9780470712184"},{"Citation":"Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of Observational Studies in Epidemiology: a proposal for reporting. Jama. 2000;283(15):2008-2012. doi:10.1001\/jama.283.15.2008"},{"Citation":"Study quality assessment tools|NHLBI, NIH. Accessed March 25, 2023. https:\/\/www.nhlbi.nih.gov\/health-topics\/study-quality-assessment-tools"},{"Citation":"Neumann I, Pantoja T, Pe\u00f1aloza B, Cifuentes L, Rada G. El sistema GRADE: Un cambio en la forma de evaluar la calidad de la evidencia y la fuerza de recomendaciones. Rev Med Chil. 2014;142(5):630-635. doi:10.4067\/S0034-98872014000500012"},{"Citation":"DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-188. doi:10.1016\/0197-2456(86)90046-2"},{"Citation":"Tufanaru C, Munn Z, Stephenson M, Aromataris E. Fixed or random effects meta-analysis? Common methodological issues in systematic reviews of effectiveness. Int J Evid Based Healthc. 2015;13(3):196-207. doi:10.1097\/XEB.0000000000000065"},{"Citation":"Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-1558. doi:10.1002\/sim.1186"},{"Citation":"Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-634. doi:10.1136\/bmj.315.7109.629"},{"Citation":"Sterne JAC, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. Br Med J. 2001;323(7304):101-105. doi:10.1136\/bmj.323.7304.101"},{"Citation":"Seashore HG. Differences between verbal and performance IQs on the Wechsler Intelligence Scale for Children. J Consult Psychol. 1951;15:62-67."},{"Citation":"Seashore HG, Wesman A, Doppelt J. The standardization of the Wechsler Intelligence Scale for Children. J Consult Psychol. 1950;14(2):99-110. doi:10.1037\/h0056307"},{"Citation":"Sato Y, Yamauchi A, Urano M, Kondo E, Saito K. Corticosteroid therapy for Duchenne muscular dystrophy: improvement of psychomotor function. Pediatr Neurol. 2014;50(1):31-37. doi:10.1016\/j.pediatrneurol.2013.07.022"},{"Citation":"Chieffo DPR, Moriconi F, Pane M, et al. A longitudinal follow-up study of intellectual function in Duchenne muscular dystrophy over age: is it really stable? J Clin Med. 2023;12(2):403. doi:10.3390\/jcm12020403"},{"Citation":"Vaillend C, Chaussenot R. Relationships linking emotional, motor, cognitive and GABAergic dysfunctions in dystrophin-deficient mdx mice. Hum Mol Genet. 2017;26(6):1041-1055. doi:10.1093\/HMG\/DDX013"},{"Citation":"Lee JS, Pfund Z, Juh\u00e1sz C, et al. Altered regional brain glucose metabolism in Duchenne muscular dystrophy: a pet study. Muscle Nerve. 2002;26(4):506-512. doi:10.1002\/mus.10238"},{"Citation":"Cyrulnik SE, Hinton VJ. Duchenne muscular dystrophy: a cerebellar disorder? Neurosci Biobehav Rev. 2008;32(3):486-496. doi:10.1016\/j.neubiorev.2007.09.001"},{"Citation":"Fatemi SH, Aldinger KA, Ashwood P, et al. Consensus paper: pathological role of the cerebellum in autism. Cerebellum. 2012;11(3):777-807. doi:10.1007\/s12311-012-0355-9"},{"Citation":"Chaussenot R, Edeline J-M, Le Bec B, El Massioui N, Laroche S, Vaillend C. Cognitive dysfunction in the dystrophin-deficient mouse model of Duchenne muscular dystrophy: a reappraisal from sensory to executive processes. Neurobiol Learn Mem. 2015;124:111-122. doi:10.1016\/j.nlm.2015.07.006"},{"Citation":"Vaillend C, Billard J-M, Laroche S. Impaired long-term spatial and recognition memory and enhanced CA1 hippocampal LTP in the dystrophin-deficient Dmdmdx mouse. Neurobiol Dis. 2004;17(1):10-20. doi:10.1016\/j.nbd.2004.05.004"},{"Citation":"Doorenweerd N, Straathof CS, Dumas EM, et al. Reduced cerebral gray matter and altered white matter in boys with Duchenne muscular dystrophy. Ann Neurol. 2014;76(3):403-411. doi:10.1002\/ana.24222"},{"Citation":"Lidov HG, Byers TJ, Watkins SC, Kunkel LM. Localization of dystrophin to postsynaptic regions of central nervous system cortical neurons. Nature. 1990;348(6303):725-728. doi:10.1038\/348725a0"},{"Citation":"Lidov HG, Kunkel LM. Dp140: alternatively spliced isoforms in brain and kidney. Genomics. 1997;45(1):132-139. doi:10.1006\/geno.1997.4905"},{"Citation":"Doorenweerd N, Mahfouz A, van Putten M, et al. Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy. Sci Rep. 2017;7(1):12575. doi:10.1038\/s41598-017-12981-5"},{"Citation":"Hoogland G, Hendriksen RGF, Slegers RJ, et al. The expression of the distal dystrophin isoforms Dp140 and Dp71 in the human epileptic hippocampus in relation to cognitive functioning. Hippocampus. 2019;29(2):102-110. doi:10.1002\/hipo.23015"},{"Citation":"Shalev H, Serlin Y, Friedman A. Breaching the blood-brain barrier as a gate to psychiatric disorder. Cardiovasc Psychiatry Neurol. 2009;2009:278531. doi:10.1155\/2009\/278531"},{"Citation":"Pereira AJ, Furlan FA. Astrocytes and human cognition: modeling information integration and modulation of neuronal activity. Prog Neurobiol. 2010;92(3):405-420. doi:10.1016\/j.pneurobio.2010.07.001"},{"Citation":"Bardoni A, Felisari G, Sironi M, et al. Loss of Dp140 regulatory sequences is associated with cognitive impairment in dystrophinopathies. Neuromuscul Disord. 2000;10(3):194-199. doi:doi:10.1016\/s0960-8966(99)00108-x"},{"Citation":"Sarig R, Mezger-Lallemand V, Gitelman I, et al. Targeted inactivation of Dp71, the major non-muscle product of the DMD gene: differential activity of the Dp71 promoter during development. Hum Mol Genet. 1999;8(1):1-10. doi:10.1093\/hmg\/8.1.1"},{"Citation":"Miranda R, Nudel U, Laroche S, Vaillend C. Altered presynaptic ultrastructure in excitatory hippocampal synapses of mice lacking dystrophins Dp427 or Dp71. Neurobiol Dis. 2011;43(1):134-141. doi:10.1016\/j.nbd.2011.02.017"},{"Citation":"Greenberg DS, Schatz Y, Levy Z, Pizzo P, Yaffe D, Nudel U. Reduced levels of dystrophin associated proteins in the brains of mice deficient for Dp71. Hum Mol Genet. 1996;5(9):1299-1303. doi:10.1093\/hmg\/5.9.1299"},{"Citation":"Haenggi T, Soontornmalai A, Schaub MC, Fritschy J-M. The role of utrophin and Dp71 for assembly of different dystrophin-associated protein complexes (DPCs) in the choroid plexus and microvasculature of the brain. Neuroscience. 2004;129(2):403-413. doi:10.1016\/j.neuroscience.2004.06.079"},{"Citation":"Nico B, Paola Nicchia G, Frigeri A, et al. Altered blood-brain barrier development in dystrophic MDX mice. Neuroscience. 2004;125(4):921-935. doi:10.1016\/j.neuroscience.2004.02.008"},{"Citation":"Jancsik V, Haj\u00f3s F. The demonstration of immunoreactive dystrophin and its developmental expression in perivascular astrocytes. Brain Res. 1999;831(1-2):200-205. doi:10.1016\/s0006-8993(99)01445-6"},{"Citation":"Kreis R, Wingeier K, Vermathen P, et al. Brain metabolite composition in relation to cognitive function and dystrophin mutations in boys with Duchenne muscular dystrophy. NMR Biomed. 2011;24(3):253-262. doi:10.1002\/nbm.1582"},{"Citation":"Latimer R, Street N, Conway KC, et al. Secondary conditions among males with Duchenne or Becker muscular dystrophy. J Child Neurol. 2017;32(7):663-670. doi:10.1177\/0883073817701368"},{"Citation":"Bitetti I, Mautone C, Bertella M, Manna MR, Varone A. Early treatment with ataluren of a 2-year-old boy with nonsense mutation Duchenne dystrophy. Acta Myol. 2021;40(4):184-186. doi:10.36185\/2532-1900-062"}]}]}}}