A novel intronic GAA repeat expansion in FGF14 causes autosomal dominant adult-onset ataxia

~ Rafehi et al., Am J Hum Gen paper, Jan 2023, Australian group describing the FGF14 repeat expansion mutation, calling it SCA50.

A randomised double-blind, cross-over trial of 4-aminopyridine for downbeat nystagmus—effects on slowphase eye velocity, postural stability, locomotion and symptoms

~Classen et al, 2021 - This paper is the basis of recent small-scale trials done using 4-AP in SCA27B patients.

Case series: Downbeat nystagmus in SCA27B

~Shirai 2023 - This is a short paper out of Japan recording downbeat nystagmus as a prominent feature of SCA27B

Clinical and genetic keys to cerebellar ataxia due to FGF14 GAA expansions

~Mereaux et al, 2024 - This paper explores the symptoms and age of onset typical of different GAA repeat lengths and the need to consider other genetic causal agents in expansions <300.

Frequency of GAA-FGF14 Ataxia in a Large Cohort of Brazilian Patients with Unsolved Adult-Onset Cerebellar Ataxia

~Novis et al, 2023 - SCA27B is also the most common cause of LOCA in Brazil. This study found SCA27B in patients of admixed American descent, European descent, and African descent.

Optimized testing strategy for the diagnosis of GAA‑FGF14 ataxia/spinocerebellar ataxia 27B

~Bonnet, 2024 - This paper goes into the specifics of genetic testing in the laboratory

Paroxysmal Ataxia- Characteristic Feature of FGF14 Repeat Expansion (SCA27B)

~Foucard, 2024 - This paper explores the episodic nature of SCA27B and the triggers that induce ataxic episodes like alcohol, exercise, stress, caffeine, and smoking.

New Study Shows DNA Sequence Protects Against SCA27B

~University of Miami news release and lay summary of Pellerin, 2024 identifies a genetic sequence that protects 2/3 of the population from the expansion of the GAA repeat in FGF14 that causes SCA27B.

4-AP improves real life gait in SCA27B single subject

~ Seemann et al, J of Neurology, July 2023 - follows 63-yr old man with SCA27B using wearable movement sensors to track improvements in gait with 4-AP treatment

Intronic FGF14 GAA repeat expansions are a common cause of ataxia syndromes with neuropathy and bilateral vestibulopathy

~Pellerin et al, 2023 - This paper finds that GAA-FGF14 related disease is a common cause of cerebellar ataxia with polyneuropathy and/or bilateral vestibulopathy (BVP). There is an overlap in symptoms between SCA27B & CANVAS.

Early Life Social Determinants of SCA6 Age of Onset, Severity, and Progression

~Chen et al, 2024 - This is an analysis of a questionnaire given to SCA6 about how life events affect symptoms of SCA6. It would be very interesting to conduct a similar study on SCA27B.

SCA27B: A novel, frequent and potentially treatable ataxia

~Pellerin et al, 2024 - This is an in-depth review of all the SCA27B research to date, published 27 JAN 24 in Clinical Translational Medicine.

FGF14 gene is a milestone in ataxia genetics

~van de Vanderburg, 2024 - This is a nice short summary of the FGF14 gene and SCA27B

Advancing molecular, phenotypic and mechanistic insights of FGF14 pathogenic expansions (SCA27B)

~Mohren 2024 (Preprint) - This paper digs deeper into the genetic mechanism underlying SCA27B

SCA27B - A Frequent Late-Onset Cerebellar Ataxia (Review)

~Clement, 2024 - This paper is a great updated review

Brain 18F-FDG PET findings and sequential vestibular testing in SCA27B: a case report

~Jimenez-Huete, 2024 - This paper follows one Spanish patient’s symptoms and corresponding brain imaging reports

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

~Char,2024 - This is the first paper about SCA27B in American patients

Intronic FGF14 GAA repeat expansions are a common cause of downbeat nystagmus syndromes: frequency, phenotypic profile, and 4-aminopyridine treatment response

~Pellerin et al, Preprint, 2023 - This paper examines the length of the FGF14 GAA repeat associated with downbeat nystagmus as well as the treatment response to 4-aminopyridine.

As Frequent as Polyglutamine Spinocerebellar Ataxias: SCA27B in a Large German Autosomal Dominant Ataxia Cohort

~Hengel et al, 2023 - This paper illustrates just how prevalent SCA27B is turning out to be.

Frequency & phenotypic spectrum of SCA27B & other genetic ataxias in Spanish Cohort of Late-Onset Cerebellar Ataxia (LOCA)

~Iruzubieta et al, 2023 - This paper gives a good look at SCA27B symptoms in Spanish patients. Like other studies, they find that SCA27B is the most common cause of LOCA.

Clinical variability associated with intronic FGF14 GAA repeat expansion in Japan

~Ando, 2024 -This paper describes SCA27B in Japan with lower prevalence than populations of European decent

RFC1 and FGF14 Repeat Expansions in Serbian Patients with Cerebellar Ataxia

~Milovanovic, 2024 - This is a study examining the prevalence of CANVAS (RFC1 expansion) and SCA27B (FGF14/GAA expansion) in the Serbian population. Researchers found two patients with early age of onset: 27 yrs (450 repeats) and 18 yrs (280 repeats).

Physical Therapy & 4AP for DBN (nystagmus)

~Cornforth & Schmahmann 2024 - This study presents how the combination of physical therapy & the drug 4-aminopyirodine (dalfampridine) can improve ataxic symptoms in people suffering from down-beat nystagmus (DBN) that is common in SCA27B

Somatic instability of the FGF14-SCA27B GAA repeat reveals a marked expansion bias in the cerebellum

~Pellerin, 2024 (Preprint) - This paper utilizes samples from blood, fibroblasts, iPS cells, and post-mortem brains to illustrate an increased GAA repeat expansion in the cerebellum compared to other tissues of the body & brain. It is hypothesized that the FGF14/GAA repeat in cerebellar neurons increases over time due to DNA single-strand breaks. DNA repairs and alternate structures formed from long GAA repeats contribute to the instability of the repeat.

GAA-FGF14 ataxia (SCA27B): phenotypic profile, natural history progression and 4-aminopyridine treatment response

~ Wilke et al, Brain, May 2023 - Examines natural history & progression of SCA27B and how the drug 4-AP can treat symptoms

Spinocerebellar ataxia 27B: episodic symptoms and acetazolamide response in 34 patients

~Ashton et al, 2023 -This paper describes the response of SCA27B patients to the drug acetazolamide. It provided some benefit to 38% of patients.

Natural History and Phenotypic Spectrum of GAA-FGF14 Sporadic Late-Onset Cerebellar Ataxia (SCA27B)

~Wirth et al, 2023 - This paper lays out a very detailed list of symptoms found in SCA27B in a cohort from France.

GAA-FGF14 Related Ataxia (SCA27B summary)

~Pellerin et al, 2024 - GeneReviews: point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.

The FGF14 GAA repeat expansion in Greek patients with late-onset cerebellar ataxia and an overview of the SCA27B phenotype across populations

~Kartanou, 2024 - A look at the prevalence, FGF14/GAA repeat expansion, and symptoms of SCA27B in Greece. SCA27B is most common known genetic cause of late-onset cerebellar ataxia (LOCA) in this population.

Oculomotor features in SCA27B patients

~Lopergolo 2024 -This is a study out of Italy about the irregular eye movement observed in patients with SCA27B

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

~Pellerin, 2024 - This paper identifies a genetic sequence that protects most of the population from incurring the expansion of the GAA repeat that leads to SCA27B

Dance as a neurorehabilitation strategy

~Aldana-Benitez 2023 - These findings suggest that dance is an innovative and effective method that can be included in therapies as it allows for a promising prognosis in motor, cognitive, and social performances of patients with neurological disorders that alter mobility and quality of life.