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:146993567-146993629

hg38

chrX:147912049-147912111

t2t

chrX:146176677-146176769

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

Location in Gene

5' UTR

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

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)

Clinical Utility and Performance of Methylation-Specific Triplet-Primed PCR for Fragile X syndrome diagnosis.

Areerat,Hnoonual, Wipawan,Arunthong, Oradawan,Plong-On, Pornsiri,Sangmanee, Pornprot,Limprasert

The Journal of molecular diagnostics : JMD · 2025-10-28

pmid:41167304

FMR1 Premutation Carrier Mothers' Daily Negative Affect and Cortisol: Probing the Impacts of Stress Exposure, Coping Style, and CGG Repeats.

Leann Smith,DaWalt, Jinkuk,Hong, Catherine Rogers,Gaspar, Ashley,Woodman, Elizabeth M,Berry-Kravis, Marsha R,Mailick

American journal on intellectual and developmental disabilities · 2025-11-01

pmid:41145158

A missense variant in the KH0-domain of FMRP downregulates the protein in a patient with the clinical hallmarks of fragile X syndrome.

Claudio Peter,D'Incal, Bram,Dierickx, Claudia,Vingerhoets, Mieke,van Haelst, Dale John,Annear, Anke,Van Dijck, Lina,Bastini, Anthony,Konings, Ellen,Elinck, Ligia,Mateiu, Agnies M,van Eeghen, R Frank,Kooy

European journal of human genetics : EJHG · 2025-10-21

pmid:41120736

Lacosamide Interaction with Expanded CGG Repeats RNA and Its Role in Modulating Poly-Glycine Protein-Mediated Toxicity in Fragile‑X Tremor/Ataxia Syndrome.

Krishna,Singh, Sakshi,Shukla, Aditi Pramod,Kumari, Amit,Kumar

ACS pharmacology & translational science · 2025-07-25

pmid:41098569

Association of Non-Coding Repeat Expansions with Parkinson's Disease Risk: Evidence from a UK Biobank-Based Whole-Genome Sequencing Study.

Zhen,Hu, Qin-Qin,Yan, Jing-Jin,Wan, Yu,Fan, Jun,Liu

Movement disorders : official journal of the Movement Disorder Society · 2025-10-11

pmid:41074692

Integrating Long-Read Nanopore Sequencing for Precision Resolution of Genomic Variants in Dystonia.

Ugo,Sorrentino, Martin,Pavlov, Nazanin,Mirza-Schreiber, Melanie,Brugger, Theresa,Brunet, Eugenia,Tsoma, Alice,Saparov, Ivana,Dzinovic, Philip,Harrer, Antonia M,Stehr, Matias,Wagner, Erik,Tilch, Barbara,Wallacher, Shiraz,Alhasan, Anne,Koy, Alessio,Di Fonzo, Miriam,Kolnikova, Katarina,Kusikova, Petra,Havrankova, Raushana,Tautanova, Sandy,Lösecke, Sebastian,Eck, Sylvia,Boesch, Jan,Necpal, Matej,Skorvanek, Robert,Jech, Holger,Prokisch, Juliane,Winkelmann, Konrad,Oexle, Elisabeth,Graf, Michael,Zech

Movement disorders : official journal of the Movement Disorder Society · 2025-09-30

pmid:41028987

Repurposing Nitazoxanide to target the expanded r(CGG)

Krishna,Singh, Sakshi,Shukla, Aditi Pramod,Kumari, Abrar,Qurashi, Arun Kumar,Verma, Amit,Kumar

International journal of biological macromolecules · 2025-09-25

pmid:41015363

Age-dependent impairment of dopamine D1 receptor signalling in mouse striatum by

Junyi,Fu, Wei,Jiang, Liping,Shen, Jiaming,Fu, Xianlai,Duan, Detian,Liu, Jingyi,Long, Shunhua,Ye, Lingjia,Tang, Yong-Hong,Yi, Yue-Sheng,Long

Brain communications · 2025-09-10

pmid:40980401

Enhanced accuracy and sensitivity in detecting FMR1 CGG repeats: a multicenter evaluation of a novel PCR-capillary electrophoresis assay.

Xin-Yi,Shou, Zhi-Wei,Zhu, Hua,Jin, Ji-Hong,Hu, Ti-Zhen,Yan, Qing-Yan,Zhong, Wen-Hao,Li, Jian-Hua,Mao, Min-Yue,Dong, Qiong,Xu, Shao-Qing,Ni

World journal of pediatrics : WJP · 2025-09-12

pmid:40940631