SCA27B FGF14

Late-onset ataxia, may have episodic onset, downbeat nystagmus, vertigo, neuropathy¹. Involvement of the superior cerebellar peduncles is frequent and may aid in diagnostic efforts².

Prevalence

Intermediate expansions 1-2% of population, but non-GAA-pure without relation to ataxia³. Found in multiple ethnicities⁴; diagnosed patients in America, Brazil, Japan, Germany, Spain, Canada, France, Austria, Australia, and Italy^3,5,6.

Age of Onset Details

Typical: 42-70; Range: 21-87^3,7.

Locus

hg19

chr13:102813924-102814076

hg38

chr13:102161574-102161726

t2t

chr13:101377549-101377792

Details

Higher repeat size is associated with earlier age of onset⁷. The 250-300 repeats range is linked to incomplete penetrance and >300 repeats with complete penetrance in some studies and resources^3,8,9. However, our thresholds are taken from suggestions made by Mohren et al upon evaluation of 169 cases and 802 controls; the authors propose lower thresholds based on pathogenic cases of shorter pure repeats⁹. Additionally, this study suggests that benign motifs may disrupt the formation of secondary structures in DNA/RNA, leading to reduced pathogenicity. The affect of interruptions on penetrance and onset has been shown in patients, with uninterrupted expansions apparently necessary for disease¹⁰. Variation in flanking regions appear to correlate with repeat size^9,11. Intermediate alleles make pose as susceptibility factors or be associated with a phenotypic spectrum (multiple system atrophy)^9,12.

Mechanism

LoF

Reduced transcript 2¹³.

Year

2023¹⁴

Location in Gene

Intron 1

Gene Strand

Alleles

Ref. Motif

GAA

Benign (ref.)

GAAGGA, GAAGAAGAAGAAGCA

Benign (gene)

CCTTCT, CTGCTTCTTCTTCTT

Pathogenic (ref.)

GAA

Pathogenic (gene)

CTT

References

Direct supporting references for info on this page.

Repeat expansion disorders.

Zhongbo,Chen, Huw R,Morris, James,Polke, Nicholas W,Wood, Sonia,Gandhi, Mina,Ryten, Henry,Houlden, Arianna,Tucci

Practical neurology · 2025-05-15

pmid:39349043

Involvement of the Superior Cerebellar Peduncles in GAA- <i>FGF14</i> Ataxia

Shihan,Chen, Catherine,Ashton, Rawan,Sakalla, Guillemette,Clement, Sophie,Planel, Céline,Bonnet, Phillipa J.,Lamont, Karthik,Kulanthaivelu, Atchayaram,Nalini, Henry,Houlden, Antoine,Duquette, Marie-Josée,Dicaire, Pablo,Iruzubieta Agudo, Javier,Ruiz-Martinez, Enrique,Marco De Lucas, Rodrigo,Sutil Berjon, Jon,Infante Ceberio, Elisabetta,Indelicato, Sylvia M.,Boesch, Matthis,Synofzik, Benjamin,Bender, Matt C.,Danzi, Stephan,Zuchner, David,Pellerin, Bernard,Brais, Mathilde,Renaud, Roberta,La Piana

Neurology Genetics · 2025-04-01

doi:10.1212/NXG.0000000000200253

genereviews:NBK599589

Neurological disorders caused by novel non-coding repeat expansions: clinical features and differential diagnosis.

Elisa,Vegezzi, Hiroyuki,Ishiura, D Cristopher,Bragg, David,Pellerin, Francesca,Magrinelli, Riccardo,Currò, Stefano,Facchini, Arianna,Tucci, John,Hardy, Nutan,Sharma, Matt C,Danzi, Stephan,Zuchner, Bernard,Brais, Mary M,Reilly, Shoji,Tsuji, Henry,Houlden, Andrea,Cortese

The Lancet. Neurology · 2024-07-01

pmid:38876750

Spinocerebellar ataxia 27B: a frequent and slowly progressive autosomal-dominant cerebellar ataxia-experience from an Italian cohort.

Sara,Satolli, Salvatore,Rossi, Elisa,Vegezzi, David,Pellerin, Maria Laura,Manca, Melissa,Barghigiani, Carla,Battisti, Giusi,Bilancieri, Giorgia,Bruno, Elena,Capacci, Carlo,Casali, Roberto,Ceravolo, Sirio,Cocozza, Stefano,Cotti Piccinelli, Chiara,Criscuolo, Matt C,Danzi, Rosa,De Micco, Giuseppe,De Michele, Marie-Josée,Dicaire, Grazia Maria Igea,Falcone, Roberto,Fancellu, Yasmine,Ferchichi, Camilla,Ferrari, Alessandro,Filla, Nicola,Fini, Alessandra,Govoni, Filomena,Lo Vecchio, Alessandro,Malandrini, Andrea,Mignarri, Olimpia,Musumeci, Claudia,Nesti, Sabina,Pappatà, Maria Teresa,Pellecchia, Alessia,Perna, Antonio,Petrucci, Maria Grazia,Pomponi, Roberta,Ravenni, Ivana,Ricca, Alessandra,Rufa, Elisabetta,Tabolacci, Alessandra,Tessa, Alessandro,Tessitore, Stephan,Zuchner, Gabriella,Silvestri, Andrea,Cortese, Bernard,Brais, Filippo M,Santorelli

Journal of neurology · 2024-06-17

pmid:38886208

An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA27B/ATX-FGF14.

Haloom,Rafehi, Justin,Read, David J,Szmulewicz, Kayli C,Davies, Penny,Snell, Liam G,Fearnley, Liam,Scott, Mirja,Thomsen, Greta,Gillies, Kate,Pope, Mark F,Bennett, Jacob E,Munro, Kathie J,Ngo, Luke,Chen, Mathew J,Wallis, Ernest G,Butler, Kishore R,Kumar, Kathy Hc,Wu, Susan E,Tomlinson, Stephen,Tisch, Abhishek,Malhotra, Matthew,Lee-Archer, Egor,Dolzhenko, Michael A,Eberle, Leslie J,Roberts, Brent L,Fogel, Norbert,Brüggemann, Katja,Lohmann, Martin B,Delatycki, Melanie,Bahlo, Paul J,Lockhart

American journal of human genetics · 2023-06-01

pmid:37267898

Clinical, Radiological and Pathological Features of a Large American Cohort of Spinocerebellar Ataxia (SCA27B).

Widad,Abou Chaar, Anirudh N,Eranki, Hannah A,Stevens, Sonya L,Watson, Darice Y,Wong, Veronica S,Avila, Megan,Delfeld, Alexander J,Gary, Sanjukta,Tawde, Malia,Triebold, Marcello,Cherchi, Tao,Xie, Paul J,Lockhart, Melanie,Bahlo, David,Pellerin, Marie-Josée,Dicaire, Matt,Danzi, Stephan,Zuchner, Bernard C,Brais, Susan,Perlman, Margit,Burmeister, Henry,Paulson, Sharan,Srinivasan, Lawrence,Schut, Matthew,Bower, Khalaf,Bushara, Chuanhong,Liao, Vikram G,Shakkottai, John,Collins, H Brent,Clark, Soma,Das, Brent L,Fogel, Christopher M,Gomez

Annals of neurology · 2024-09-12

pmid:39263992

Intronic

David,Pellerin, Carlo,Wilke, Andreas,Traschütz, Sara,Nagy, Riccardo,Currò, Marie-Josée,Dicaire, Hector,Garcia-Moreno, Mathieu,Anheim, Thomas,Wirth, Jennifer,Faber, Dagmar,Timmann, Christel,Depienne, Dan,Rujescu, José,Gazulla, Mary M,Reilly, Paola,Giunti, Bernard,Brais, Henry,Houlden, Ludger,Schöls, Michael,Strupp, Andrea,Cortese, Matthis,Synofzik

Journal of neurology, neurosurgery, and psychiatry · 2024-01-11

pmid:37399286

Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions.

Lars,Mohren, Friedrich,Erdlenbruch, Elsa,Leitão, Fabian,Kilpert, G Sebastian,Hönes, Sabine,Kaya, Christopher,Schröder, Andreas,Thieme, Marc,Sturm, Joohyun,Park, Agatha,Schlüter, Montserrat,Ruiz, Moisés,Morales de la Prida, Carlos,Casasnovas, Kerstin,Becker, Ulla,Roggenbuck, Sonali,Pechlivanis, Frank J,Kaiser, Matthis,Synofzik, Thomas,Wirth, Mathieu,Anheim, Tobias B,Haack, Paul J,Lockhart, Karl-Heinz,Jöckel, Aurora,Pujol, Stephan,Klebe, Dagmar,Timmann, Christel,Depienne

Nature communications · 2024-09-03

pmid:39227614

Targeted Long-Read Sequencing as a Single Assay Improves the Diagnosis of Spastic-Ataxia Disorders.

Laura Ivete,Rudaks, Igor,Stevanovski, Dennis,Yeow, Andre L M,Reis, Sanjog R,Chintalaphani, Pak Leng,Cheong, Hasindu,Gamaarachchi, Lisa,Worgan, Kate,Ahmad, Michael,Hayes, Andrew,Hannaford, Samuel,Kim, Victor S C,Fung, Gabor M,Halmagyi, Andrew,Martin, David,Manser, Michel,Tchan, Karl,Ng, Marina L,Kennerson, Ira W,Deveson, Kishore Raj,Kumar

Annals of clinical and translational neurology · 2025-02-25

pmid:40007153

A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus.

David,Pellerin, Giulia F,Del Gobbo, Madeline,Couse, Egor,Dolzhenko, Sathiji K,Nageshwaran, Warren A,Cheung, Isaac R L,Xu, Marie-Josée,Dicaire, Guinevere,Spurdens, Gabriel,Matos-Rodrigues, Igor,Stevanovski, Carolin K,Scriba, Adriana,Rebelo, Virginie,Roth, Marion,Wandzel, Céline,Bonnet, Catherine,Ashton, Aman,Agarwal, Cyril,Peter, Dan,Hasson, Nadejda M,Tsankova, Ken,Dewar, Phillipa J,Lamont, Nigel G,Laing, Mathilde,Renaud, Henry,Houlden, Matthis,Synofzik, Karen,Usdin, Andre,Nussenzweig, Marek,Napierala, Zhao,Chen, Hong,Jiang, Ira W,Deveson, Gianina,Ravenscroft, Schahram,Akbarian, Michael A,Eberle, Kym M,Boycott, Tomi,Pastinen, Bernard,Brais, Stephan,Zuchner, Matt C,Danzi

Nature genetics · 2024-06-27

pmid:38937606

Frequency of FGF14 intronic GAA repeat expansion in patients with multiple system atrophy and undiagnosed ataxia in the Japanese population.

Toshiyuki,Kakumoto, Kenta,Orimo, Takashi,Matsukawa, Jun,Mitsui, Tomohiko,Ishihara, Osamu,Onodera, Yuta,Suzuki, Shinichi,Morishita, Tatsushi,Toda, Shoji,Tsuji

European journal of human genetics : EJHG · 2024-11-27

pmid:39604554

Deep Intronic

David,Pellerin, Matt C,Danzi, Carlo,Wilke, Mathilde,Renaud, Sarah,Fazal, Marie-Josée,Dicaire, Carolin K,Scriba, Catherine,Ashton, Christopher,Yanick, Danique,Beijer, Adriana,Rebelo, Clarissa,Rocca, Zane,Jaunmuktane, Joshua A,Sonnen, Roxanne,Larivière, David,Genís, Laura,Molina Porcel, Karine,Choquet, Rawan,Sakalla, Sylvie,Provost, Rebecca,Robertson, Xavier,Allard-Chamard, Martine,Tétreault, Sarah J,Reiling, Sara,Nagy, Vikas,Nishadham, Meera,Purushottam, Seena,Vengalil, Mainak,Bardhan, Atchayaram,Nalini, Zhongbo,Chen, Jean,Mathieu, Rami,Massie, Colin H,Chalk, Anne-Louise,Lafontaine, François,Evoy, Marie-France,Rioux, Jiannis,Ragoussis, Kym M,Boycott, Marie-Pierre,Dubé, Antoine,Duquette, Henry,Houlden, Gianina,Ravenscroft, Nigel G,Laing, Phillipa J,Lamont, Mario A,Saporta, Rebecca,Schüle, Ludger,Schöls, Roberta,La Piana, Matthis,Synofzik, Stephan,Zuchner, Bernard,Brais

The New England journal of medicine · 2022-12-14

pmid:36516086

An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA50/ATX-FGF14.

American journal of human genetics · 2022-12-08

pmid:36493768

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)

First Report of Co-Occurring FGF14 (SCA27B) and RFC1 (CANVAS) Repeat Expansions in Two of Three Siblings with Late-Onset Cerebellar Ataxia.

Tasos,Tsokkos, Kyproula,Christodoulou, Christina,Votsi, Anthi,Georghiou, Andrea,Christofides, Astero,Constantinou, Eleni,Zamba-Papanicolaou

Cerebellum (London, England) · 2025-10-21

pmid:41118032

Clinical characteristics, cerebellar MR spectroscopy and response to 3,4-diaminopyridine in spinocerebellar ataxia 27B: the Sheffield Ataxia Centre experience.

Ikechukwu,Chukwuocha, David,Pellerin, Priya,Shanmugarajah, Theocharis,Tsironis, Emma,Foster, Nigel,Hoggard, Nick,Beauchamp, Lauren,Turton, Alisdair,McNeill, Bernard,Brais, Marios,Hadjivassiliou

Journal of neurology · 2025-10-09

pmid:41065930

Video head impulse test differentiates RFC1-CANVAS, FGF14-SCA27B, and idiopathic late-onset cerebellar ataxias.

Leonardo E,Ariello, Daniel R,Gold, Jennifer L,Millar, Michael C,Schubert, Weiyi,Mu, Liana,Rosenthal, David P W,Rastall

Journal of neurology · 2025-10-07

pmid:41055766

Delineating the pathogenic threshold and phenotypic spectrum of SCA27B: findings from a large French-Canadian cohort.

Pablo,Iruzubieta, David,Pellerin, Catherine,Ashton, Felipe,Villa, Mathilde,Renaud, Marie-Josée,Dicaire, Matt C,Danzi, Mayra,Aldecoa, Jean,Mathieu, Rami,Massie, Colin H,Chalk, Anne-Louise,Lafontaine, François,Evoy, Marie-France,Rioux, Jean-Denis,Brisson, Kym M,Boycott, Henry,Houlden, Matthis,Synofzik, Roberta,La Piana, Stephan,Zuchner, Antoine,Duquette, Bernard,Brais

Journal of neurology · 2025-09-20

pmid:40974444

Ocular Motor and Vestibular Profile in Spinocerebellar Ataxia Type 27B: Toward a Practical Bedside Diagnostic Framework.

Leonardo Eleuterio,Ariello, Daniel R,Gold, Weiyi,Mu, Michael C,Schubert, Claire,Allen, Ashley,Paul, David P W,Rastall

Cerebellum (London, England) · 2025-09-04

pmid:40906330

Repeat-associated ataxias in a German patient cohort analysed by targeted parallel long-read sequencing.

Hannes,Erdmann, Annalisa,Schaub, Morghan C,Lucas, Veronika,Scholz, Anna,Benet-Pages, Kerstin,Becker, Christine,Dineiger, Veronika,Mayer, Inga,van Buren, Eva,Breithausen, Karl,Akbari, Isabell,Cordts, Mayra,Sauer, Christine,Schneider, Rosanna,Krakowsky, Franziska,Schnabel, Konstanze,Dunker, Lena,Fabritius, Johannes,Gerb, Denis,Grabova, Ken,Möhwald, Marius,Näher, Karoline,Steinmetz, Franziska,Thiessen, Alexander,Jäck, Christiane,Schneider-Gold, Simone,Zittel, Christina,Petersen, Isolde,Schreyer, Larissa,Mämecke, Sibylle,Wilfling, Gilbert,Wunderlich, David,Brenner, Yorck,Hellenbroich, Kirsten,Muhle, Tessa,Huchtemann, Inga,Claus, Thomas,Klopstock, Michael,Strupp, Johannes,Levin, Günter,Höglinger, Doreen,Huppert, Sandra,Becker-Bense, Filipp,Filippopulos, Fabian,Kilpert, Elsa,Leitão, Sabine,Kaya, Christel,Depienne, Florian,Schöberl, Teresa,Neuhann, Elke,Holinski-Feder, Andreas,Zwergal, Angela,Abicht

Brain : a journal of neurology · 2025-09-03

pmid:40898875

Long-read sequencing identifies

Fulya,Akçimen, Kensuke,Daida, Lara M,Lange, Abraham,Moller, Abigail,Miano-Burkhardt, Laksh,Malik, Kimberly,Paquette, Pilar Alvarez,Jerez, Jackson,Mingle, Breeana,Baker, Melissa,Meredith, Cedric,Kouam, Paige,Jarreau, Androo,Markham, Jessica,Anderson, Miten,Jain, Mark,Chaisson, Mark,Cookson, Bradford,Casey, Hirotaka,Iwaki, Sara,Bandres-Ciga, Paula,Saffie-Awad, Mike,Nalls, Zih-Hua,Fang, Andrew B,Singleton, Cornelis,Blauwendraat, Kimberley J,Billingsley

medRxiv : the preprint server for health sciences · 2025-08-19

pmid:40894141

GAA-FGF14 Expansions and CACNA1A Variants: Phenotypic Overlap and Diagnostic Implications.

Elisabetta,Indelicato, Zofia,Fleszar, David,Pellerin, Wolfgang,Nachbauer, Stephan,Zuchner, Andreas,Traschütz, Matthias,Amprosi, Ludger,Schöls, Tobias B,Haack, Bernard,Brais, Sylvia,Boesch, Matthis,Synofzik

Movement disorders : official journal of the Movement Disorder Society · 2025-08-19

pmid:40879304

Unstable FGF14 GAA repeat expansions in Indian ataxia patients: a broader phenotype and involvement of modifier loci?

Pannaga,Prasad G, Aleksandra,Makarova, Kandasamy,Kathirvel, Suleyman,Gulsuner, Tomas,Walsh, Shreevidya,Parthaje, Chinu,Patra, Bhagyalakshmi,Shankarappa, Shridhar,Utagi, Vaishnavi,Desai, Vikram,Holla, Nitish,Kamble, Ravi,Yadav, Atchayaram,Nalini, Biju,Viswanath, Marie-Claire,King, Sanjeev,Jain, Pramod Kumar,Pal, Meera,Purushottam

Journal of human genetics · 2025-08-20

pmid:40835733