FRDA FXN

Disease ID
FRDA
Gene ID
FXN
Updated
Feb 5, 2025
v2.2.1

Disease

Name
Friedreich ataxia
Inheritance
Autosomal recessive
Description
Any Friedreich ataxia in which the cause of the disease is a mutation in the FXN gene1 .
Prevalence
1 50,000
1/50,0002,3 : Known carrier frequency 1000/100,000; observed 421/100,000. Most common inherited ataxia in Europe, the Middle East, India, and North Africa; not documented in Southeast Asia, in sub-Saharan Africa, or among Native Americans4 .
Age of Onset(Typical)Years2  8010  15
Age of Onset Details
Typical: 10-15; Range: 2-804 .

Locus

Details
96% of FA patients have biallelic GAA expansions in intron 1 (compared to compound heterozygous with another mutation type), in which the reference allele is conventionally 5-33 repeats4 . Intermediate alleles (34-55) are associated with premutations, but may lead to disease as exact pathogenicity/penetrance thresholds have not been demarcated4 . The expanded repeats can interrupted either with GAAGAG, GAAGGA, or GAAGAAAA sequences, leading to differential phenotypes5 . Allele size is correlated with disease severity and inversely correlated to age of onset, and expansions can reach 1700 repeats6 .
Mechanism
LoF
Loss of function via transcriptional silencing7,8 .
Year
19969
Location in Gene
Intron 1
Gene Strand

Alleles

Ref. Motif
GAA
Pathogenic (ref.)
GAA
Pathogenic (gene)
AAG
BenignIntermediatePathogenicUnits5  3334  5556  1,700

gnomAD

References

Direct supporting references for info on this page.

1
Ontology Lookup Service (OLS)
mondo:0100340
3
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
5
Sequence variation in GAA repeat expansions may cause differential phenotype display in Friedreich's ataxia.
D O,McDaniel, B,Keats, V V,Vedanarayanan, S H,Subramony
Movement disorders : official journal of the Movement Disorder Society · 2001-11-01
pmid:11748752
6
Clinical and genetic abnormalities in patients with Friedreich's ataxia.
A,Dürr, M,Cossee, Y,Agid, V,Campuzano, C,Mignard, C,Penet, J L,Mandel, A,Brice, M,Koenig
The New England journal of medicine · 1996-10-17
pmid:8815938
7
Diseases of unstable repeat expansion: mechanisms and common principles.
Jennifer R,Gatchel, Huda Y,Zoghbi
Nature reviews. Genetics · 2005-10-01
pmid:16205714
8
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
9
Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion.
V,Campuzano, L,Montermini, M D,Moltò, L,Pianese, M,Cossée, F,Cavalcanti, E,Monros, F,Rodius, F,Duclos, A,Monticelli, F,Zara, J,Cañizares, H,Koutnikova, S I,Bidichandani, C,Gellera, A,Brice, P,Trouillas, G,De Michele, A,Filla, R,De Frutos, F,Palau, P I,Patel, S,Di Donato, J L,Mandel, S,Cocozza, M,Koenig, M,Pandolfo
Science (New York, N.Y.) · 1996-03-08
pmid:8596916

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)

Diagnosis of hereditary ataxias: a real-world single center experience.
Adriana,Meli, Vincenzo,Montano, Giovanni,Palermo, Antonella,Fogli, Anna,Rocchi, Annalisa Lo,Gerfo, Rossella,Maltomini, Ludovica,Cori, Antonio,Siniscalchi, Clara,Bernardini, Giulia,Cecchi, Gabriele,Siciliano, Roberto,Ceravolo, Maria Adelaide,Caligo, Michelangelo,Mancuso, Piervito,Lopriore
Journal of neurology · 2025-01-15
pmid:39812846
Friedreich Ataxia: An (Almost) 30-Year History After Gene Discovery.
Massimo,Pandolfo
Neurology. Genetics · 2025-01-13
pmid:39810753
Friedreich ataxia: what can we learn from non-GAA repeat mutations?
David R,Lynch, M,Shen, Robert B,Wilson
Neurodegenerative disease management · 2025-01-15
pmid:39810561
Assessment of the Clinical Interactions of GAA Repeat Expansions in
Brandon J,Gerhart, David,Pellerin, Matt C,Danzi, Stephan,Zuchner, Bernard,Brais, Gabriel,Matos-Rodrigues, Andre,Nussenzweig, Karen,Usdin, Courtney C,Park, Jill S,Napierala, David R,Lynch, Marek,Napierala
Neurology. Genetics · 2024-11-20
pmid:39574782
Screening for SCA27B, CANVAS and other repeat expansion disorders in Greek patients with late-onset cerebellar ataxia suggests a need to update current diagnostic algorithms.
Georgios,Koutsis, Chrisoula,Kartanou, Zoi,Kontogeorgiou, Chrysoula,Koniari, Alexandros,Mitrousias, David,Pellerin, Marie-Jose,Dicaire, Pablo,Iruzubieta, Matt C,Danzi, Konstantinos,Athanassopoulos, Nikolaos,Ragazos, Maria,Stamelou, Michail,Rentzos, Evangelos,Anagnostou, Stephan,Zuchner, Bernard,Brais, Henry,Houlden, Marios,Panas, Leonidas,Stefanis, Georgia,Karadima
Journal of the neurological sciences · 2024-11-15
pmid:39571249
Differential Gene Expression in Late-Onset Friedreich Ataxia: A Comparative Transcriptomic Analysis Between Symptomatic and Asymptomatic Sisters.
Sara,Petrillo, Alessia,Perna, Andrea,Quatrana, Gabriella,Silvestri, Enrico,Bertini, Fiorella,Piemonte, Massimo,Santoro
International journal of molecular sciences · 2024-10-29
pmid:39519164
Uniparental IsoDisomy: a case study on a new mechanism of Friedreich ataxia.
Brian,Sperelakis-Beedham, Cyril,Gitiaux, Marine,Rajaoba, Maryse,Magen, Nicolas,Derive, Jerome,Chansard, Jean-Madeleine,de Sainte Agathe, Marie-Laure,Maurin, Zahra,Assouline, Christine,Barnerias, Isabelle,Desguerre, Julie,Steffann, Giulia,Barcia
European journal of human genetics : EJHG · 2024-11-04
pmid:39496895
Case Report of Friedreich's Ataxia and ALG1 -Related Biochemical Abnormalities in a Patient With Progressive Spastic Paraplegia.
Aisling,Quinlan, Lance,Rodan, Elizabeth,Barkoudah, Amy,Tam, Afshin,Saffari, Ibrahim,Shammas, Wasantha,Ranatunga, Eva,Morava-Kozicz, Devin,Oglesbee, Gerald,Berry, Darius,Ebrahimi-Fakhari, Siddharth,Srivastava
American journal of medical genetics. Part A · 2024-09-26
pmid:39324476
Unusual Age-Dependent Behavior of Leukocytes Telomere Length in Friedreich's Ataxia.
Daniela,Scarabino, Liana,Veneziano, Suran,Nethisinghe, Elide,Mantuano, Alessia,Fiore, Giulia,Granata, Nita,Solanky, Ginevra,Zanni, Francesca,Cavalcanti, Rosa Maria,Corbo, Paola,Giunti
Movement disorders : official journal of the Movement Disorder Society · 2024-09-05
pmid:39235665