Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia with associated limb muscle weakness, absent lower limb reflexes, extensor plantar responses, dysarthria, and decreased vibratory sense and proprioception. Onset is usually in the first or second decade, before the end of puberty¹.

Prevalence

1 50,000

1/50,000^1,2: 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 Americans³.

Age of Onset

Typical: 10-15; Range: 2-80³.

HPO Terms

–

Association

Mendelian

Locus

hg19 chr9:71652202-71652220

hg38 chr9:69037286-69037304

t2t chr9:81210834-81210861

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 repeats³. Intermediate alleles (34-55) are associated with premutations, but may lead to disease as exact pathogenicity/penetrance thresholds have not been demarcated³. The expanded repeats can be interrupted with GAAGAG, GAAGGA, or GAAGAAAA sequences, leading to differential phenotypes⁴. Allele size is correlated with disease severity and inversely correlated to age of onset, and expansions can reach 1700 repeats⁵.

Mechanism

LoF

Loss of function via transcriptional silencing^6,7.

Detection

RP-PCR and long-range PCR have been used to detect expansions [@pmid:35595154]. Long-read sequencing has sized large alleles and resolved sequence organization [@pmid:35595154].

Year

1996⁸

Location in Gene

Intron 1

Gene Strand

Alleles

Ref. Motif

GAA

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

GAA

Pathogenic (gene)

AAG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

gnomAD

References

Direct supporting references for info on this page.

1omim:229300

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

Friedreich Ataxia

Sanjay I.,Bidichandani, Martin B.,Delatycki, Marek,Napierala, Antoine,Duquette

GeneReviews® · 1993-01-01

genereviews:NBK1281

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

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

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

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)

Therapeutic activity of a hematopoietic stem cell-delivered cell-penetrating frataxin in Friedreich's ataxia models.

Jeffrey,Pido-Lopez, Shefta E,Moula, Enas,Shaban, Konstantinos,Stamatiou, Bethan J,Critchley, Thomas E,Whittaker, Stina,Svensson, Sara,Anjomani-Virmouni, Ester,Kalef-Ezra, Lucinda,Carr, Jane,Hassel, Adrian J,Thrasher, Manju A,Kurian, Ian A,Blair, Teerapat,Rojsajjakul, Giorgia,Santilli, Arturo,Sala

Cell reports. Medicine · 2026-05-13

pmid:42134333

Genome-wide detection and clinical prioritization of tandem repeat outliers using long-read sequencing.

Sophia B,Gibson, Nikhita,Damaraju, J Gus,Gustafson, Elsa V,Balton, Sirisak,Chanprasert, Ian A,Glass, Martha,Horike-Pyne, Runjun D,Kumar, Kathleen A,Leppig, Chris,Lundberg, Jane,Ranchalis, Elisabeth A,Rosenthal, Andrew K,Solomon, Andrew B,Stergachis, Mark,Wener, Gail P,Jarvik, Elizabeth E,Blue, Katrina M,Dipple, Harriet,Dashnow, Lea M,Starita, Danny E,Miller

medRxiv : the preprint server for health sciences · 2026-05-01

pmid:42094143

The TRKB Agonist 7,8-dihydroxyflavone Alleviates DNA Damage and Apoptosis in a Neuronal Cell Model of Friedreich's Ataxia.

Jorge,Galán-Cruz, Andrés,Vicente-Acosta, Frida,Loría, Javier,Díaz-Nido, Saúl,Herranz-Martín

Molecular neurobiology · 2026-04-22

pmid:42018061

Longitudinal analysis shows GAA1 length and baseline clinical status as robust predictors of progression in Friedreich ataxia.

Leire,Manrique, Francisco,Martínez-Dubarbie, Ana L,Pelayo-Negro, Natalia,Benitez-Calle, María Victoria,Sanchez-Pelaez, Daniel,Cota-Gonzalez, Ruben,Loza, Raquel,Martinez-Díaz, Juan,Irure-Ventura, Coro,Sanchez-Quintana, Ivelisse,Sanchez, Antoni,Matilla-Dueñas, Jon,Infante

Journal of neurology · 2026-04-09

pmid:41954755

Peripheral frataxin levels govern long-term clinical progression in Friedreich ataxia.

Christian,Rummey, Ian A,Blair, Clementina,Mesaros, Teerapat,Rojsajjakul, Yina,Dong, George,Wilmot, Theresa,Zesiewicz, Kathy,Mathews, Joseph C,Hoyle, Lauren,Seeberger, Louise A,Corben, Martin Bruce,Delatycki, Richard S,Finkel, Richard H,Roxburgh, Antoine,Duquette, Grace,Yoon, Christopher M,Gomez, S H,Subramony, Susan,Perlman, Shana,Mccormack, David R,Lynch

BMJ neurology open · 2026-03-23

pmid:41919005

Friedreich ataxia transcriptomic dysregulation and identification of cell type-specific biomarkers: A systematic review and meta-analysis.

Marnie L,Maddock, Sara,Miellet, Anjila,Dongol, Amy J,Hulme, Chloe K,Kennedy, Louise A,Corben, Rocio K,Finol-Urdaneta, Alberto,Nettel-Aguirre, Chiara,Dionisi, Martin B,Delatycki, Joel M,Gottesfeld, Massimo,Pandolfo, Elisabetta,Soragni, Sanjay I,Bidichandani, Jarmon G,Lees, Shiang Y,Lim, Jill S,Napierala, Marek,Napierala, Mirella,Dottori

bioRxiv : the preprint server for biology · 2026-03-20

pmid:41890103

Diagnostic yield of genome sequencing in children with progressive movement disorders.

Luca,Schierbaum, Enrique,Gonzalez Saez-Diez, Amy,Tam, Joshua,Rong, Umar,Zubair, Katerina,Bernardi, Kathryn,Yang, Vicente,Quiroz, Zainab,Zaman, Afshin,Saffari, Siofra,Carty, Habibah A P,Agianda, Sanda,Alexandrescu, Florian,Eichler, Abigail,Sveden, Maya,Chopra, Daniel G,Calame, Matt C,Danzi, Stephan,Zuchner, Darius,Ebrahimi-Fakhari

Brain : a journal of neurology · 2026-02-05

pmid:41640354

Unrecognized high prevalence of expanded composite repeats in Friedreich ataxia.

Morgan C,Devore, Christina,Lam, Graham,Wiley, Courtney C,Park, David R,Lynch, Sanjay I,Bidichandani

Human molecular genetics · 2026-02-10

pmid:41432640

The role of disease-associated short tandem repeats in amyotrophic lateral sclerosis.

Joke J F A,van Vugt, Ramona A J,Zwamborn, Egor,Dolzhenko, Michael A,Eberle, Ben,Weisburd, Erwin,Bekema, Maarten,Kooyman, Bi-Nan,Wang, Erik-Jan,Kamsteeg, Monique,Losekoot, Frank,Baas, Camilla,Novy, Helle,Høyer, Ruben P A,van Eijk, Michael A,van Es, Wouter,van Rheenen, Ammar,Al-Chalabi, Leonard H,van den Berg, Jan H,Veldink

Brain communications · 2025-12-09

pmid:41426430

Locus FRDA FXN

Disease

Locus

Alleles

gnomAD

References

Additional Literature