title: Autosomal recessive spastic ataxia of Charlevoix-Saguenay: compound heterozygotes for nonsense mutations of the SACS gene.
abstract: Mutations of the SACS gene have been reported in patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay from Canada (Quebec), Tunisia, Japan, Turkey, Belgium, Italy, Spain, the Netherlands, and Germany. Features that distinguish autosomal recessive spastic ataxia of Charlevoix-Saguenay from other recessive ataxias include sensory motor polyneuropathy and hypermyelinated retinal nerve fibers. We describe the clinical, electrophysiological, and radiological features in 2 white American siblings diagnosed with autosomal recessive spastic ataxia of Charlevoix-Saguenay. The 2 affected children are compound heterozygotes for nonsense mutations of the SACS gene (c. 3484 G>T, p. E 1162 X; and c. 11,707 C>T, p. R 3903 X). We have measured allele-specific SACS mRNA abundance in peripheral blood and show that these specific mutant mRNAs are not degraded. We suggest that in children with early onset cerebellar ataxia and spasticity, ophthalmological examination and nerve conduction testing may guide genetic testing.
authors: St Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA. Vinodh.Narayanan@chw.edu
authors: Vinodh
authors: V
authors: Narayanan
authors: Stephen G
authors: SG
authors: Rice
authors: Shannon S
authors: SS
authors: Olfers
authors: Kumaraswamy
authors: K
authors: Sivakumar
mesh_terms: D002648:Child; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D009128:Muscle Spasticity / Q000150:complications / Q000235:genetics*; D009431:Neural Conduction / Q000235:genetics; D012333:RNA, Messenger; D020754:Spinocerebellar Ataxias / Q000150:complications / Q000151:congenital* / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; C404403:SACS protein, human