학술논문

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation.
Document Type
Academic Journal
Author
Tassone F; Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA.; MIND Institute, University of California Davis, Davis, CA 95817, USA.; Protic D; Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11129 Belgrade, Serbia.; Fragile X Clinic, Special Hospital for Cerebral Palsy and Developmental Neurology, 11040 Belgrade, Serbia.; Allen EG; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.; Archibald AD; Victorian Clinical Genetics Services, Royal Children's Hospital, Melbourne, VIC 3052, Australia.; Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC 3052, Australia.; Genomics in Society Group, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC 3052, Australia.; Baud A; Department of Gene Expression, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Uniwersytetu Poznańskiego 6, 61-614 Poznan, Poland.; Brown TW; Central Clinical School, University of Sydney, Sydney, NSW 2006, Australia.; Fragile X Association of Australia, Brookvale, NSW 2100, Australia.; NYS Institute for Basic Research in Developmental Disabilities, New York, NY 10314, USA.; Budimirovic DB; Department of Psychiatry, Fragile X Clinic, Kennedy Krieger Institute, Baltimore, MD 21205, USA.; Department of Psychiatry & Behavioral Sciences-Child Psychiatry, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.; Cohen J; Fragile X Alliance Clinic, Melbourne, VIC 3161, Australia.; Dufour B; MIND Institute, University of California Davis, Davis, CA 95817, USA.; Department of Pathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children of Northern California, School of Medicine, University of California Davis, Sacramento, CA 95817, USA.; Eiges R; Stem Cell Research Laboratory, Medical Genetics Institute, Shaare Zedek Medical Center Affiliated with the Hebrew University School of Medicine, Jerusalem 91031, Israel.; Elvassore N; Veneto Institute of Molecular Medicine (VIMM), 35129 Padova, Italy.; Department of Industrial Engineering, University of Padova, 35131 Padova, Italy.; Gabis LV; Keshet Autism Center Maccabi Wolfson, Holon 5822012, Israel.; Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel.; Grudzien SJ; Department of Neurology, University of Michigan, 4148 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.; Hall DA; Department of Neurological Sciences, Rush University, Chicago, IL 60612, USA.; Hessl D; MIND Institute, University of California Davis, Davis, CA 95817, USA.; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California Davis, Sacramento, CA 95817, USA.; Hogan A; Department of Communication Sciences and Disorders, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA.; Hunter JE; RTI International, Research Triangle Park, NC 27709, USA.; Jin P; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.; Jiraanont P; Faculty of Medicine, King Mongkut's Institute of Technology Ladkrabang, Bangkok 10520, Thailand.; Klusek J; Department of Communication Sciences and Disorders, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA.; Kooy RF; Department of Medical Genetics, University of Antwerp, 2000 Antwerp, Belgium.; Kraan CM; Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC 3052, Australia.; Diagnosis and Development, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.; Laterza C; Veneto Institute of Molecular Medicine (VIMM), 35129 Padova, Italy.; Department of Industrial Engineering, University of Padova, 35131 Padova, Italy.; Lee A; Fragile X New Zealand, Nelson 7040, New Zealand.; Lipworth K; Fragile X Association of Australia, Brookvale, NSW 2100, Australia.; Losh M; Roxelyn and Richard Pepper Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL 60201, USA.; Loesch D; School of Psychology and Public Health, La Trobe University, Melbourne, VIC 3086, Australia.; Lozano R; Departments of Genetics and Genomic Sciences and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Mailick MR; Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.; Manolopoulos A; Intramural Research Program, Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD 21224, USA.; Martinez-Cerdeno V; MIND Institute, University of California Davis, Davis, CA 95817, USA.; Department of Pathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children of Northern California, School of Medicine, University of California Davis, Sacramento, CA 95817, USA.; McLennan Y; Department of Pathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children of Northern California, School of Medicine, University of California Davis, Sacramento, CA 95817, USA.; Miller RM; National Fragile X Foundation, Washington, DC 20005, USA.; Montanaro FAM; Child and Adolescent Neuropsychiatry Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.; Department of Education, Psychology, Communication, University of Bari Aldo Moro, 70121 Bari, Italy.; Mosconi MW; Schiefelbusch Institute for Life Span Studies, University of Kansas, Lawrence, KS 66045, USA.; Clinical Child Psychology Program, University of Kansas, Lawrence, KS 66045, USA.; Kansas Center for Autism Research and Training (K-CART), University of Kansas, Lawrence, KS 66045, USA.; Potter SN; RTI International, Research Triangle Park, NC 27709, USA.; Raspa M; RTI International, Research Triangle Park, NC 27709, USA.; Rivera SM; Department of Psychology, University of Maryland, College Park, MD 20742, USA.; Shelly K; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.; Todd PK; Department of Neurology, University of Michigan, 4148 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.; Ann Arbor Veterans Administration Healthcare, Ann Arbor, MI 48105, USA.; Tutak K; Department of Gene Expression, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Uniwersytetu Poznańskiego 6, 61-614 Poznan, Poland.; Wang JY; Center for Mind and Brain, University of California Davis, Davis, CA 95618, USA.; Wheeler A; RTI International, Research Triangle Park, NC 27709, USA.; Winarni TI; Center for Biomedical Research (CEBIOR), Faculty of Medicine, Universitas Diponegoro, Semarang 502754, Central Java, Indonesia.; Zafarullah M; Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA.; Hagerman RJ; MIND Institute, University of California Davis, Davis, CA 95817, USA.; Department of Pediatrics, School of Medicine, University of California Davis, Sacramento, CA 95817, USA.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
Subject
Language
English
Abstract
The premutation of the fragile X messenger ribonucleoprotein 1 ( FMR1 ) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.