FXS FMR1

A genetic syndrome caused by mutations in the FMR1 gene which is responsible for the expression of the fragile X mental retardation 1 protein. This protein participates in neural development. This syndrome is manifested with mental, emotional, behavioral, physical, and learning disabilities.; Any primary ovarian failure in which the cause of the disease is a mutation in the FMR1 gene.; Fragile X-associated tremor/ataxia syndrome (FXTAS) is a rare neurodegenerative disorder characterized by adult-onset progressive intention tremor and gait ataxia^1,2,3.

Prevalence

14 100,000

Incidence of full mutation in males 19/100,000; prevalence 14/100,000⁴. Female prevalence 9/100,000⁵. Known carrier frequency is approximately 300-500/100,000 but detected was 11/100,000⁶. FXS prevalence 1:7000 males, 1:11,000 females; FX premutation carriers 1:290-855 males, 1:148-300 females⁷. Found worldwide⁴. In Thailand, 1 in 600 women carry a premutation, and 1 in 400 carry a 'gray zone' allele⁸.

Age of Onset Details

Typical: FXS 1 to 'first several years of life', FXTAS 60-65⁴; Range: 0⁹- 78¹⁰; detailed description of typical symptom onset and diagnosis available from Arnold et al⁷.

Locus

hg19

chrX:146993555-146993629

hg38

chrX:147912037-147912111

t2t

chrX:146176665-146176769

Details

Intermediate or 'gray zone' occur at 45-54 alleles and may be unstable enough to expand into the premutation range, as well as associate with parkinsonism^11,4. FXTAS/POI occurs at 55-200 repeats, FXS >200, late onset; AGG and CTG interruptions documented^4,12.

Mechanism

LoF/GoF

Loss of function via transcriptional silencing in FXS, RNA gain of function in FXTAS/FXPOI^13,14.

Year

1992¹⁵; causative gene discovered in 1991¹⁶

Gene Strand

Alleles

Ref. Motif

CGG

Pathogenic (ref.)

CGG

Pathogenic (gene)

CGG

gnomAD

Sex

Pathogenic Genotype (%): % of individuals predicted to be affected based on their genotype

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0010383

Ontology Lookup Service (OLS)

mondo:0010706

Ontology Lookup Service (OLS)

mondo:0010382

FMR1 Disorders

Jessica Ezzell,Hunter, Elizabeth,Berry-Kravis, Heather,Hipp, Peter K.,Todd

GeneReviews® · 1993-01-01

genereviews:NBK1384

Epidemiology of fragile X syndrome: a systematic review and meta-analysis.

Jessica,Hunter, Oliver,Rivero-Arias, Angel,Angelov, Edward,Kim, Iain,Fotheringham, Jose,Leal

American journal of medical genetics. Part A · 2014-04-03

pmid:24700618

Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes.

Haibao,Tang, Ewen F,Kirkness, Christoph,Lippert, William H,Biggs, Martin,Fabani, Ernesto,Guzman, Smriti,Ramakrishnan, Victor,Lavrenko, Boyko,Kakaradov, Claire,Hou, Barry,Hicks, David,Heckerman, Franz J,Och, C Thomas,Caskey, J Craig,Venter, Amalio,Telenti

American journal of human genetics · 2017-11-02

pmid:29100084

isbn:978-3-031-66932-3

Population-based FMR1 carrier screening among reproductive women.

Quratul,Ain, Ye Hyun,Hwang, Daryl,Yeung, Pacharee,Panpaprai, Wiwat,Iamurairat, Wiboon,Chutimongkonkul, Objoon,Trachoo, Flora,Tassone, Poonnada,Jiraanont

Journal of assisted reproduction and genetics · 2024-09-25

pmid:39320553

UpToDate

url:https://www.uptodate.com/contents/fragile-x-syndrome-clinical-features-and-diagnosis-in-children-and-adolescents

CGG repeat length correlates with age of onset of motor signs of the fragile X-associated tremor/ataxia syndrome (FXTAS).

Flora,Tassone, John,Adams, Elizabeth M,Berry-Kravis, Susannah S,Cohen, Alfredo,Brusco, Maureen A,Leehey, Lexin,Li, Randi J,Hagerman, Paul J,Hagerman

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2007-06-05

pmid:17427188

Fragile X Gray Zone Alleles Are Associated With Signs of Parkinsonism and Earlier Death.

Deborah A,Hall, Sukriti,Nag, Bichun,Ouyang, David A,Bennett, Yuanqing,Liu, Aisha,Ali, Lili,Zhou, Elizabeth,Berry-Kravis

Movement disorders : official journal of the Movement Disorder Society · 2020-05-28

pmid:32463542

Detecting AGG Interruptions in Females With a FMR1 Premutation by Long-Read Single-Molecule Sequencing: A 1 Year Clinical Experience.

Simon,Ardui, Valerie,Race, Thomy,de Ravel, Hilde,Van Esch, Koenraad,Devriendt, Gert,Matthijs, Joris R,Vermeesch

Frontiers in genetics · 2018-05-16

pmid:29868108

Diseases of unstable repeat expansion: mechanisms and common principles.

Jennifer R,Gatchel, Huda Y,Zoghbi

Nature reviews. Genetics · 2005-10-01

pmid:16205714

Clinical and neuroimaging review of triplet repeat diseases.

Ryo,Kurokawa, Mariko,Kurokawa, Akihiko,Mitsutake, Moto,Nakaya, Akira,Baba, Yasuhiro,Nakata, Toshio,Moritani, Osamu,Abe

Japanese journal of radiology · 2022-09-28

pmid:36169768

Molecular studies of the fragile X syndrome.

S J,Knight, M C,Hirst, A,Roche, Z,Christodoulou, S M,Huson, R,Winter, M,Fitchett, M J,McKinley, R H,Lindenbaum, Y,Nakahori

American journal of medical genetics

pmid:1605194

Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome.

A J,Verkerk, M,Pieretti, J S,Sutcliffe, Y H,Fu, D P,Kuhl, A,Pizzuti, O,Reiner, S,Richards, M F,Victoria, F P,Zhang

Cell · 1991-05-31

pmid:1710175

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Novel p.Arg534del Mutation and MTHFR C667T Polymorphism in Fragile X Syndrome (FXS) With Autism Spectrum Phenotype: A Case Report.

Hasan,Hasan, Ellery R,Santos, Seyedeh Ala Mokhtabad,Amrei, Flora,Tassone, Jamie Leah,Randol, Paul,Hagerman, Randi J,Hagerman

Case reports in genetics · 2025-01-13

pmid:39839505

Trinucleotide Repeat Expansion and RNA Dysregulation in Fragile X Syndrome: Emerging Therapeutic Approaches.

Suna,Jung, Joel D,Richter

RNA (New York, N.Y.) · 2024-12-26

pmid:39725461

Ascorbic Acid Ameliorates Molecular and Developmental Defects in Human-Induced Pluripotent Stem Cell and Cerebral Organoid Models of Fragile X Syndrome.

Keith M,Gunapala, Aseel,Gadban, Faiza,Noreen, Primo,Schär, Nissim,Benvenisty, Verdon,Taylor

International journal of molecular sciences · 2024-11-26

pmid:39684429

Genetics architecture of spontaneous coronary artery dissection in an Italian cohort.

Marta,Casula, Daniela,Marchetti, Lucia,Trevisan, Laura,Pezzoli, Matteo,Bellini, Serena,Patrone, Antonio,Zingarelli, Fabio,Gotta, Maria,Iascone, Paola,Mandich

Frontiers in cardiovascular medicine · 2024-11-25

pmid:39654947

Parkinson's Disease Polygenic Risk Score and Neurological Involvement in Carriers of the FMR1 Premutation Allele: A Case for Genetic Modifier.

Danuta Z,Loesch, Freddy,Chafota, Minh Q,Bui, Elsdon,Storey, Anna,Atkinson, Nicholas G,Martin, Scott D,Gordon, Miguel E,Rentería, Randi J,Hagerman, Flora,Tassone

Molecular genetics & genomic medicine · 2024-11-01

pmid:39588919

Repeat expansion in a Fragile X model is independent of double strand break repair mediated by Pol θ, Rad52, Rad54l or Rad54b.

Bruce E,Hayward, Geum-Yi,Kim, Carson J,Miller, Cai,McCann, Megan G,Lowery, Richard D,Wood, Karen,Usdin

bioRxiv : the preprint server for biology · 2024-11-06

pmid:39574643

Dampened α7 nAChR activity contributes to audiogenic seizures and hyperactivity in a mouse model of Fragile X Syndrome.

Sarah,Goebel, Dylann,Cordova-Martinez, Vytas K,Verselis, Anna,Francesconi

bioRxiv : the preprint server for biology · 2024-11-03

pmid:39553953

dmTGS: Precise Targeted Enrichment Long-Read Sequencing Panel for Tandem Repeat Detection.

Kang,Yang, Yue,Liu, Ji,Zhang, Qian,Yu, Feng,Xu, Jiyuan,Liu, Yuting,Li, Xiaojie,Zhang, Zhiqiang,Wang, Ning,Wang, Yuezhen,Li, Yan,Shi, Wan-Jin,Chen

Clinical chemistry · 2024-11-04

pmid:39492694

Prevalence and implications of fragile X premutation screening in Thailand.

Areerat,Hnoonual, Sunita,Kaewfai, Chanin,Limwongse, Pornprot,Limprasert

Scientific reports · 2024-11-01

pmid:39482338