Abstract Details

Title Prevalence of FGF14-mediated Spinocerebellar Ataxia 27B (SCA27B) in a United States Cohort

Topic Movement Disorders

Presentation(s) P6 - Poster Session 6 (11:45 AM-12:45 PM)

Poster/Presentation
Number 5-015

Objective Repeat expansions in the FGF14 gene cause spinocerebellar ataxia 27B (SCA27B), a slowly progressive adult-onset cerebellar ataxia. This may be a common genetic cause of adult-onset ataxia, with cohort studies suggesting diagnostic rates of between 10-61% in various populations worldwide, however, prevalence studies have yet to be performed in the United States.

Background An estimated 50% of patients with genetic cerebellar ataxia remain undiagnosed despite rigorous genetic testing, most likely due to genetic etiologies undetectable by current genetic testing.

Design/Methods A cohort of 732 predominantly adult-onset patients with undiagnosed cerebellar ataxia was evaluated and excluded for common genetic causes. Average age was 56.4 years (±16.8 years, range: 1-89 years), gender was 52.5% female, and the ancestral makeup was 71.7% white, 9.6% Asian, 2.7% Black, 1.0% Native American, with 8.1% of Hispanic/Latino ethnicity. Patients were screened with long-range and bidirectional repeat-primed PCR and products were analyzed by capillary and agarose gel electrophoresis to identify expanded FGF14 alleles and determine their approximate size.

Results Repeat expansions of ≥250 GAA tandem repeats were observed in 55 patients (7.5%) within the cohort. Of these 55 expansions, 31 (56%, 4.2% of cohort) were deemed fully pathogenic, with uninterrupted expansions >300 GAA tandem repeats, and 24 (44%, 3.3% of cohort) were designated low-penetrance pathogenicity, with uninterrupted expansions between 250-300 GAA tandem repeats. Clinically, of the 55 patients with diagnostic findings, 45 (81.8%) experienced unsteadiness, 45 (81.8%) demonstrated gait ataxia, 33 (60%) had episodic onset of symptoms, 27 (49.1%) experienced dizziness, 26 (47.2%) showed saccadic pursuit of eye movements, and 24 (43.6%) showed cerebellar atrophy on MRI.

Conclusions In a large undiagnosed ataxia patient cohort from the U.S. comprised of 732 individuals, repeat expansions of ≥250 FGF14-GAA tandem repeats were observed in 7.5%. Testing for SCA27B should be strongly considered in all adult undiagnosed ataxia patients, particularly those with episodic onset.

Authors/Disclosures
Anirudh Eranki, Student PRESENTER	Mr. Eranki has nothing to disclose.
Hannah A. Stevens, MS	Ms. Stevens has nothing to disclose.
Sonya Watson, MS CGC	Miss Watson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Marinus Pharmaceuticals.
Veronica Avila	Ms. Avila has nothing to disclose.
Darice Y. Wong, PhD	The institution of an immediate family member of Dr. Wong has received research support from NIH.
Brent L. Fogel, MD, PhD, FAAN (UCLA Neurology)	Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for National Ataxia Foundation. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Ataxia Global Initiative. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Today. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Genetics. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Genetics. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Genes. Dr. Fogel has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neuromarkers. The institution of Dr. Fogel has received research support from the National Institutes of Health. The institution of Dr. Fogel has received research support from the National Ataxia Foundation. The institution of an immediate family member of Dr. Fogel has received research support from the National Institutes of Health, the National Science Foundation, and the Department of Defense. The institution of Dr. Fogel has received research support from US Department of Defense .

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