Abstract Details

Title Phenotype Description and Lower Pathogenicity Threshold in a Large Cohort of SCA27B

Topic Movement Disorders

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

Poster/Presentation
Number 5-028

Objective To describe a large cohort of patients with pathogenic expansions in FGF14 from Quebec, Canada.

Background Spinocerebellar ataxia 27B (SCA27B) is an autosomal dominant ataxia caused by an intronic GAA repeat expansion in FGF14. The pathogenic threshold is considered above 250 GAA repeats with incomplete penetrance and above 300 GAA repeats with full penetrance. Scarce reports suggest a lower pathogenic threshold.

Design/Methods We clinically evaluated and performed in-depth phenotyping of individuals followed in our clinic carrying an FGF14 (GAA)_≥250 allele and we conducted segregation studies in large families.

Results We identified 136 affected individuals from 64 families who carried an FGF14 (GAA)_≥250 allele, with a mean of 381 repeats (range, 250–716). 117 were French Canadian. 111 of the patients with updated data were symptomatic (111/122, 91%). Thirteen of them had only episodic symptoms at last examination (13/111, 12%), although 77% (86/111) had episodic symptoms at disease onset. Episodic symptoms included ataxia (52/86, 60%), diplopia (40/86, 47%), dysarthria (34/86, 40%), and vertigo (24/86, 28%), frequently combined. Mean age at onset of episodic symptoms was 52.6 (range, 27-87) and it correlated inversely with the repeat size (Pearson -0.367, p = 0.001). Mean age of permanent symptoms was 58.7 and also correlated inversely with repeat size (Pearson -0.5084, p <0.0001). Interestingly, we also identified 20 affected patients with an expansion between 200-249. Although its pathogenicity is difficult to determine, some of them show a compatible phenotype, ie. episodic onset in 13 or downbeat nystagmus in six. Five of them had a positive family history of SCA27B.

Conclusions SCA27B is commonly associated with a episodic onset before the permanent ataxia. Our results show a correlation between repeat size and age of onset. This series provide evidence that even lower threshold may be pathogenic, although further research and precised criteria are needed.

Authors/Disclosures
Pablo Iruzubieta, MD, PhD (Donostia University Hospital) PRESENTER	Dr. Iruzubieta has received personal compensation in the range of $0-$499 for serving as a Participant in an activity with UCB. Dr. Iruzubieta has received personal compensation in the range of $500-$4,999 for serving as a Teacher in a course with Health in Code.
Catherine Ashton, MBBS (Catherine Ashton)	Dr. Ashton has nothing to disclose.
David Pellerin, MD	Dr. Pellerin has nothing to disclose.
Felipe Villa, MD (McGill University)	Dr. Villa has nothing to disclose.
Matt Danzi (University of Miami)	Matt Danzi has nothing to disclose.
Marie-Josee Dicaire	Marie-Josee Dicaire has nothing to disclose.
Mayra Aldecoa, MD	Ms. Aldecoa has nothing to disclose.
Mathilde Renaud, MD, PhD	Prof. Renaud has nothing to disclose.
Jean Mathieu, MD	Dr. Mathieu has nothing to disclose.
Rami Massie, MD (McGill University)	Dr. Massie has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Gowlingwlg. Dr. Massie has received personal compensation in the range of $500-$4,999 for serving as a Lecturer with Pfizer. Dr. Massie has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board with Argenx.
Colin H. Chalk, MD (Montreal General Hospital)	Dr. Chalk has nothing to disclose.
Anne L. Lafontaine, MD (Montreal Neurological Institute)	Dr. Lafontaine has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Paladin. Dr. Lafontaine has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sunovion. Dr. Lafontaine has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie.
Francois Evoy, MD (University of Sherbrooke)	Dr. Evoy has nothing to disclose.
Marie-France Rioux, MD	Dr. Rioux has nothing to disclose.
Jean-Denis Brisson, MD (Dr Jean-Denis Brisson inc)	Dr. Brisson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AbbVie. Dr. Brisson has received research support from Pharnext, Harmony biosciences, PepGen.
Kym Boycott	No disclosure on file
Stephan Zuchner, MD, FAAN (University of Miami School of Medicine)	Dr. Zuchner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Applied Therapeutics. The institution of Dr. Zuchner has received research support from Muscular Dystrophy Association. The institution of Dr. Zuchner has received research support from CMT Association. Dr. Zuchner has received intellectual property interests from a discovery or technology relating to health care.
Roberta La Piana (McGill University)	Roberta La Piana has received research support from Canadian Institute Health Research. Roberta La Piana has received research support from Ataxia Canada. Roberta La Piana has received research support from Spastic Paraplegia Foundation. Roberta La Piana has received research support from Fonds de Recherche en Santé du Quebec. Roberta La Piana has received research support from Roche Canada. Roberta La Piana has received research support from ARSACS Foundation.
Antoine Duquette, MD (CHUM)	Dr. Duquette has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Reata. The institution of Dr. Duquette has received research support from Actelion. The institution of Dr. Duquette has received research support from Ataxia Canada/FARA.
Bernard Brais, MD	Dr. Brais has nothing to disclose.

��ɫ��

��ɫ��