{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:56:03Z","timestamp":1777442163165,"version":"3.51.4"},"reference-count":15,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Victorian Government's Operational Infrastructure Support Program"},{"name":"Murdoch Childrens Research Institute"},{"DOI":"10.13039\/100014607","name":"Royal Children's Hospital Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014607","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NHMRC Development Grant","award":["1017263"],"award-info":[{"award-number":["1017263"]}]},{"name":"Pierce Armstrong Trust"},{"name":"NHMRC Project Grant","award":["104299"],"award-info":[{"award-number":["104299"]}]},{"name":"NHMRC Project Grant","award":["1103389"],"award-info":[{"award-number":["1103389"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec><jats:label\/><jats:p>CGG repeat expansion &gt;200 within <jats:italic>FMR1<\/jats:italic>, termed full mutation (FM), has been associated with promoter methylation, consequent silencing of gene expression and fragile X syndrome (FXS)\u2014a common cause of intellectual disability and co\u2010morbid autism. Unmethylated premutation (55\u2013199 repeats) and FM alleles have been associated with fragile X related tremor\/ataxia syndrome (FXTAS), a late onset neurodegenerative disorder. Here we present a 33\u2010year\u2010old male with FXS, with white matter changes and progressive deterioration in gait with cerebellar signs consistent with probable FXTAS; there was no evidence of any other cerebellar pathology. We show that he has tissue mosaicism in blood, saliva, and buccal samples for the size and methylation of his expanded alleles and a de novo, unmethylated microdeletion. This microdeletion involves a \u223c80\u2009bp sequence in the <jats:italic>FMR1<\/jats:italic> promoter as well as complete loss of the CGG repeat in a proportion of cells. Despite <jats:italic>FMR1<\/jats:italic> mRNA levels in blood within the normal range, the methylation and CGG sizing results are consistent with the diagnosis of concurrent FXS and probable FXTAS. The demonstrated presence of unmethylated FM alleles would explain the manifestation of milder than expected cognitive and behavioral impairments and early onset of cerebellar ataxia. Our case suggests that individuals with FXS, who manifest symptoms of FXTAS, may benefit from more detailed laboratory testing. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37954","type":"journal-article","created":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T10:23:15Z","timestamp":1475835795000},"page":"3327-3332","source":"Crossref","is-referenced-by-count":22,"title":["Partially methylated alleles, microdeletion, and tissue mosaicism in a fragile X male with tremor and ataxia at 30 years of age: A case report"],"prefix":"10.1002","volume":"170","author":[{"given":"Yun Tae","family":"Hwang","sequence":"first","affiliation":[{"name":"Department of Neurology Gosford Hospital Gosford New South Wales Australia"},{"name":"Institute of Neurology University College London London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solange Mabel","family":"Aliaga","sequence":"additional","affiliation":[{"name":"Cyto\u2010Molecular Diagnostic Research Laboratory Victorian Clinical Genetics Services and Murdoch Childrens Research Institute Royal Children's Hospital Melbourne Victoria Australia"},{"name":"Faculty of Medicine Dentistry and Health Sciences University of Melbourne Parkville Victoria Australia"},{"name":"Molecular and Cytogenetics Laboratory  INTA University of Chile Santiago Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Arpone","sequence":"additional","affiliation":[{"name":"Cyto\u2010Molecular Diagnostic Research Laboratory Victorian Clinical Genetics Services and Murdoch Childrens Research Institute Royal Children's Hospital Melbourne Victoria Australia"},{"name":"Faculty of Medicine Dentistry and Health Sciences University of Melbourne Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Francis","sequence":"additional","affiliation":[{"name":"Cyto\u2010Molecular Diagnostic Research Laboratory Victorian Clinical Genetics Services and Murdoch Childrens Research Institute Royal Children's Hospital Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Cyto\u2010Molecular Diagnostic Research Laboratory Victorian Clinical Genetics Services and Murdoch Childrens Research Institute Royal Children's Hospital Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Belinda","family":"Chong","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory Victorian Clinical Genetics Services and Murdoch Childrens Research Institute Royal children's Hospital Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard Robert","family":"Slater","sequence":"additional","affiliation":[{"name":"Cyto\u2010Molecular Diagnostic Research Laboratory Victorian Clinical Genetics Services and Murdoch Childrens Research Institute Royal Children's Hospital Melbourne Victoria Australia"},{"name":"Faculty of Medicine Dentistry and Health Sciences University of Melbourne Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn","family":"Rogers","sequence":"additional","affiliation":[{"name":"Genetics of Learning Disability Service, Hunter Genetics Waratah New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lesley","family":"Bretherton","sequence":"additional","affiliation":[{"name":"Department of Psychology Royal Children's Hospital Melbourne Victoria Australia"},{"name":"Melbourne School of Psychological Sciences University of Melbourne Parkville Melbourne Australia"},{"name":"Child Neuropsychology Murdoch Childrens Research Institute Royal Children's Hospital Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Hunter","sequence":"additional","affiliation":[{"name":"Genetics of Learning Disability Service, Hunter Genetics Waratah New South Wales Australia"},{"name":"Faculty of Medicine University of Newcastle Newcastle New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Heard","sequence":"additional","affiliation":[{"name":"Department of Neurology Gosford Hospital Gosford New South Wales Australia"},{"name":"Westmead Millennium Institute University of Sydney Westmead New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Eugeny","family":"Godler","sequence":"additional","affiliation":[{"name":"Cyto\u2010Molecular Diagnostic Research Laboratory Victorian Clinical Genetics Services and Murdoch Childrens Research Institute Royal Children's Hospital Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1084-8592(98)80044-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5254.1423"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2011.177626"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq037"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-0317"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.4.460"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8166-1-5"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2005.00425.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3182064362"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01675.x"},{"key":"e_1_2_7_12_1","volume-title":"Autism 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