Two RFC1 splicing variants in CANVAS.

We screened the I RFC1 i gene by fluorescent duplex PCR, repeat primer-PCR, and long range-PCR with Southern blotting of the PCR product, as previously described.[7] The patient carried an expanded (AAGGG) SB n sb allele and an allele of normal length with 10 pentaplets. We read with great interest the original article ' I RFC1 i nonsense and frameshift variants cause CANVAS: clues for an unsolved pathophysiology' by Benkirane I et al. i [1] Biallelic I RFC1 i (AAGGG) SB n sb expansions are responsible for cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), a frequent cause of late-onset ataxia, with sporadic or autosomal recessive inheritance.[2] Since their discovery, other pathogenic pentanucleotide motifs have been reported in the literature.[[3], [5]] The authors reported two cases of heterozygous compound truncating variants of I RFC1 i in two patients with CANVAS. Screening for Friedreich ataxia showed an expanded allele of 1000 triplets and a normal allele without other pathogenic variants shown by Sanger sequencing and MLPA of the I FXN i gene. Previous genetic screening of the I POLG i and I DMPK i genes, dystrophic myotonia and episodic ataxia panel genes ( I CACNA1A i , I CLCN1 i , I KNJ2 i , I KCN1A i ) by next-generation sequencing (NGS), and polyglutamine expansions in the I ATXN1 i , I ATXN2 i , I ATXN3 i , I CACNA1A i , I ATXN7 i and I TBP i genes were negative. [Extracted from the article]