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Abstract Details

A Novel Late-onset Dominant Episodic Ataxia in a Large French Canadian Kindred
Movement Disorders
P8 - Poster Session 8 (8:00 AM-9:00 AM)
3-011

To report a large French Canadian family with a novel form of late-onset episodic ataxia (EA) characterized by variable expressivity.
The EAs are a heterogenous group of dominantly inherited disorders. Eight subtypes have been described, among which a genetic cause has been established in EA1, EA2 and EA6 only. Other forms were defined according to mapped genetic loci or shared clinical features. A sizeable proportion of EA cases presenting in late adulthood still awaits mutation identification. 

Phenotyping was performed through serial clinical evaluations, brain MRI and nerve conduction studies. Whole exome and genome sequencing were obtained in three patients. Linkage analysis was performed using SNP genotype data of 8 affected and 11 unaffected family members. Haplotype mapping using microsatellites and copy number variant analyses were performed on genomic regions of interest. Genome-wide screening for putative repeat expansions is currently underway.
Sixteen individuals belonging to a French Canadian family presented with recurrent attacks of ataxia often triggered by alcohol or physical activity. Attack frequency varied from once daily to weekly, while duration varied from 5-180min. More than 90% developed progressive ataxia. The mean age of onset was 58.2 years for the first episode, and 62.3 years for the progression of ataxia. The ataxia was of variable severity with SARA scores varying between 1 and 18. Interictal downbeat nystagmus was observed in 80% of individuals. Brain MRI showed mild-to-moderate cerebellar atrophy in permanently ataxic cases. Next generation sequencing failed to reveal a shared potentially pathogenic rare variant. Mutations in known EA genes, including in CACNB4, were excluded. Linkage analysis identified 4 candidate loci with LOD scores >2, one of which was excluded using microsatellite-based haplotype mapping. 

This study describes a novel and variable form of late-onset progressive EA in a French Canadian family. Efforts are underway to identify the underlying causative mutation.
Authors/Disclosures
David Pellerin, MD
PRESENTER 		Dr. Pellerin has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Marie-Josee Dicaire Marie-Josee Dicaire has nothing to disclose.
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.
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.
No disclosure on file
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 (Montreal Neurological Institute-Hospital) Dr. Brais has nothing to disclose.