Browse by author
Lookup NU author(s): Dr Angela Pyle, Dr Helen GriffinORCiD, Dr Jennifer Duff, Shona Bennett, Dr Simon Zwolinski, Tania Smertenko, Dr Patrick Yu Wai Man, Dr Mauro Santibanez Koref, Professor Rita HorvathORCiD, Professor Patrick Chinnery
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
The molecular diagnosis of adult-onset autosomal recessive cerebellar ataxias remains challenging because of genetic heterogeneity. However, recently developed molecular genetic techniques will potentially revolutionize the diagnostic approach. Here we set out to defi ne the genetic basis of the ataxia in two brothers with no molecular diagnosis. Clinical evaluation was followed by whole-exome second-generation sequencing and comparative genomic hybridization to determine the diagnosis. Whole-exome sequencing identifi ed a hemizygous novel spastic ataxia of Charlevoix-Saguenay (SACS) stop-codon mutation in both brothers (c.13048G -> T, p.E4350*) that was present in the mother, but not the father. Comparative genomic hybridization revealed a 0.7-Mb deletion on chromosome 13q12.12 in both brothers, which included SACS and was heterozygous in the asymptomatic father. The milder phenotype, caused by a whole-gene deletion and a stop-codon mutation in SACS, indicates a loss-of-function mechanism in late-onset autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), and illustrates the importance of chromosomal rearrangements in the investigation of adult-onset ataxia.
Author(s): Pyle A, Griffin H, Duff J, Bennett S, Zwolinski S, Smertenko T, Yu-Wai-Man P, Santibanez-Koref M, Horvath R, Chinnery PF
Publication type: Article
Publication status: Published
Journal: Journal of Neurogenetics
Year: 2013
Volume: 27
Issue: 4
Pages: 176-182
Print publication date: 01/12/2013
ISSN (print): 0167-7063
ISSN (electronic): 1563-5260
Publisher: Informa Healthcare
URL: http://dx.doi.org/10.3109/01677063.2013.831094
DOI: 10.3109/01677063.2013.831094
Altmetrics provided by Altmetric
