{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:00:25Z","timestamp":1760241625268,"version":"build-2065373602"},"reference-count":23,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2018,6,7]],"date-time":"2018-06-07T00:00:00Z","timestamp":1528329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Financial Markets Foundation for Children","award":["2017-361"],"award-info":[{"award-number":["2017-361"]}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["104299 and 1103389"],"award-info":[{"award-number":["104299 and 1103389"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Next Generation Clinical Researchers Program - Career Development Fellowship-Funded by the Medical Research Future Fund","award":["1141334"],"award-info":[{"award-number":["1141334"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Fragile X syndrome (FXS) is usually associated with a CGG repeat expansion &gt;200 repeats within the FMR1 gene, known as a full mutation (FM). FM alleles produce abnormal methylation of the FMR1 promoter with reduction or silencing of FMR1 gene expression. Furthermore, premutation (PM: 55\u2013199 CGGs) and full mutation alleles usually expand in size when maternally transmitted to progeny. This study describes a PM allele carried by the mother decreasing to a normal sized allele in a male from a dichorionic diamniotic (DCDA) twin pregnancy, with the female twin inheriting FM (200\u2013790 CGGs), PM (130 CGGs) and normal-sized (39 CGGs) alleles. Further evidence of instability of the maternal PM allele was shown by a male proband (older brother) mosaic for PM (CGG 78 and 150 CGGs) and FM (200\u2013813 CGGs), and a high level of FMR1 promoter methylation, between 50 and 70%, in multiple tissues. The fully-retracted, normal-sized allele was identified by PCR CGG sizing in the male twin, with no evidence of a FM allele identified using Southern blot analysis in multiple tissues collected postnatally and prenatally. Consistent with this, prenatal PCR sizing (35 CGGs) showed inconsistent inheritance of the maternal normal allele (30 CGGs), with single-nucleotide polymorphism (SNP) linkage analysis confirming that the abnormal FMR1 chromosome had been inherited from the mother\u2019s PM chromosome. Importantly, the male twin showed no significant hypermethylation of the FMR1 promoter in all pre and postnatal tissues tested, as well as normal levels of FMR1 mRNA in blood. In summary, this report demonstrates the first postnatal follow up of a prenatal case in which FMR1 mRNA levels were approaching normal, with normal levels of FMR1 promoter methylation and normal CGG size in multiple pre and postnatally collected tissues.<\/jats:p>","DOI":"10.3390\/genes9060287","type":"journal-article","created":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T03:13:18Z","timestamp":1528427598000},"page":"287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Prenatal Diagnosis of Fragile X Syndrome in a Twin Pregnancy Complicated by a Complete Retraction"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3052-947X","authenticated-orcid":false,"given":"Yael","family":"Prawer","sequence":"first","affiliation":[{"name":"Monash Genetics, Monash Health, Clayton, 3168 Victoria, Australia"},{"name":"Department of Paediatrics, Monash University, Clayton, 3168 Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2475-6545","authenticated-orcid":false,"given":"Matthew","family":"Hunter","sequence":"additional","affiliation":[{"name":"Monash Genetics, Monash Health, Clayton, 3168 Victoria, Australia"},{"name":"Department of Paediatrics, Monash University, Clayton, 3168 Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Cronin","sequence":"additional","affiliation":[{"name":"Cyto-Molecular Diagnostic Research Laboratory, Victorian Clinical Genetics Services and Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Parkville, 3052 Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Ling","sequence":"additional","affiliation":[{"name":"Cyto-Molecular Diagnostic Research Laboratory, Victorian Clinical Genetics Services and Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Parkville, 3052 Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solange","family":"Aliaga Vera","sequence":"additional","affiliation":[{"name":"Cyto-Molecular Diagnostic Research Laboratory, Victorian Clinical Genetics Services and Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Parkville, 3052 Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Fahey","sequence":"additional","affiliation":[{"name":"Monash Genetics, Monash Health, Clayton, 3168 Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikki","family":"Gelfand","sequence":"additional","affiliation":[{"name":"Monash Genetics, Monash Health, Clayton, 3168 Victoria, Australia"},{"name":"Department of Paediatrics, Monash University, Clayton, 3168 Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph","family":"Oertel","sequence":"additional","affiliation":[{"name":"Cyto-Molecular Diagnostic Research Laboratory, Victorian Clinical Genetics Services and Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Parkville, 3052 Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Essra","family":"Bartlett","sequence":"additional","affiliation":[{"name":"Cyto-Molecular Diagnostic Research Laboratory, Victorian Clinical Genetics Services and Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Parkville, 3052 Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Francis","sequence":"additional","affiliation":[{"name":"Cyto-Molecular Diagnostic Research Laboratory, Victorian Clinical Genetics Services and Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Parkville, 3052 Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6405-269X","authenticated-orcid":false,"given":"David","family":"Godler","sequence":"additional","affiliation":[{"name":"Cyto-Molecular Diagnostic Research Laboratory, Victorian Clinical Genetics Services and Murdoch Childrens Research Institute, Royal Children\u2019s Hospital, Parkville, 3052 Victoria, Australia"},{"name":"Dentistry and Health Sciences, Department of Paediatrics, Faculty of Medicine, University of Melbourne, Parkville, 3052 Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1542\/peds.2008-0317","article-title":"Advances in the treatment of fragile X 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Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1373\/clinchem.2013.217331","article-title":"Early detection of fragile X syndrome: Applications of a novel approach for improved quantitative methylation analysis in venous blood and newborn blood spots","volume":"60","author":"Inaba","year":"2014","journal-title":"Clin. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1097\/GIM.0b013e3182064362","article-title":"Evidence for the toxicity of bidirectional transcripts and mitochondrial dysfunction in blood associated with small CGG expansions in the FMR1 gene in patients with parkinsonism","volume":"13","author":"Loesch","year":"2011","journal-title":"Genet. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kraan, C.M., Cornish, K.M., Bui, Q.M., Li, X., Slater, H.R., and Godler, D.E. (2018). \u03b2-glucuronidase use as a single internal control gene may confound analysis in FMR1 mRNA toxicity studies. 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A"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/9\/6\/287\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:07:46Z","timestamp":1760195266000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/9\/6\/287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,7]]},"references-count":23,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,6]]}},"alternative-id":["genes9060287"],"URL":"https:\/\/doi.org\/10.3390\/genes9060287","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2018,6,7]]}}}