{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:07:12Z","timestamp":1790370432823,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"NICHD","doi-asserted-by":"publisher","award":["HD036071"],"award-info":[{"award-number":["HD036071"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"NICHD","doi-asserted-by":"publisher","award":["P50 HD103526"],"award-info":[{"award-number":["P50 HD103526"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MIND Institute Intellectual and Developmental Disabilities Research Center","award":["HD036071"],"award-info":[{"award-number":["HD036071"]}]},{"name":"MIND Institute Intellectual and Developmental Disabilities Research Center","award":["P50 HD103526"],"award-info":[{"award-number":["P50 HD103526"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We investigated the molecular and clinical profile of five boys carrying the fragile X messenger ribonucleoprotein 1 (FMR1) mutation and who suffered from the effects of prenatal alcohol exposure. Fragile X syndrome (FXS) testing was performed using PCR and Southern Blot analysis, and fragile X messenger ribonucleoprotein protein (FMRP) expression levels were measured by Western blot analysis. Clinical evaluation included cognitive functions, adaptive skills, autism phenotype, and severity of behavior measures. Fetal Alcohol Spectrum Disorder (FASD) was also assessed. Five adopted male siblings were investigated, four of which (cases 1, 2, 3, and 4) were diagnosed with FXS, FASD, and ASD, and one, the fraternal triplet (case 5), was diagnosed with FASD and ASD and no FXS. The molecular profile of case 1 and 2 showed the presence of a hypermethylated full mutation (FM) and the resulting absence of FMRP. Cases 3 and 4 (identical twins) were FM-size mosaics (for the presence of an FM and a deleted allele), resulting in 16% and 50% FMRP expression levels, respectively. FMRP expression level was normal in case 5 (fraternal twin). Severe behavioral problems were observed in all cases, including aggression, tantrum, self-harming, anxiety, and defiant behavior, due to different mutations of the FMR1 gene, in addition to biological exposure, home environmental factors, and potentially to additional background gene effects.<\/jats:p>","DOI":"10.3390\/ijms26072840","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T07:25:00Z","timestamp":1742541900000},"page":"2840","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In Utero Alcohol and Unsuitable Home Environmental Exposure Combined with FMR1 Full Mutation Allele Cause Severe Fragile X Syndrome Phenotypes"],"prefix":"10.3390","volume":"26","author":[{"given":"Tri Indah","family":"Winarni","sequence":"first","affiliation":[{"name":"Center for Biomedical Research (CEBIOR), Faculty of Medicine, Universitas Diponegoro, Semarang 50275, Central Java, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5749-1248","authenticated-orcid":false,"given":"Ramkumar","family":"Aishworiya","sequence":"additional","affiliation":[{"name":"Khoo Teck Puat-National University Children\u2019s Medical Institute, National University Health System, Singapore 119074, Singapore"},{"name":"Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Culpepper","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1856-0535","authenticated-orcid":false,"given":"Marwa","family":"Zafarullah","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guadalupe","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanaporn Jasmine","family":"Wilaisakditipakorn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California Davis School of Medicine, Sacramento, CA 95817, USA"},{"name":"MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narueporn","family":"Likhitweerawong","sequence":"additional","affiliation":[{"name":"MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Law","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California Davis School of Medicine, Sacramento, CA 95817, USA"},{"name":"MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-8448","authenticated-orcid":false,"given":"Randi","family":"Hagerman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California Davis School of Medicine, Sacramento, CA 95817, USA"},{"name":"MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6388-9180","authenticated-orcid":false,"given":"Flora","family":"Tassone","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, CA 95817, USA"},{"name":"MIND Institute, University of California Davis Medical Center, Sacramento, CA 95817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1002\/ajmg.a.32439","article-title":"Co-occurring conditions associated with FMR1 gene variations: Findings from a national parent survey","volume":"146A","author":"Bailey","year":"2008","journal-title":"Am. 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