Adellgene® SCAs

Spinocerebellar ataxias (SCAs) are a heterogeneous group of hereditary neurodegenerative disorders that mainly affect the cerebellum, leading to progressive loss of coordination and balance. These diseases are autosomal dominant and are characterized by a wide clinical and genetic variability.

At least twelve types of SCAs are caused by expansions of repetitions, among which six result from mutations caused by the expansion of the CAG trinucleotide which encodes polyglutamine stretches in proteins associated with these diseases: SCA1, SCA2, SCA3/Machado-Joseph disease, SCA6, SCA7, and SCA17. SCA12 is also caused by the expansion of the CAG trinucleotide, although the mutation is found in the 5′ UTR region of the gene. Additionally, another disorder related to a translated repetition of the CAG trinucleotide, dentatorubral-pallidoluysian atrophy (DRPLA), is classified as an SCA due to its clinical characteristics.

INTENDED USED

Adellgene® SCAs is a semi-automated in vitro diagnostic kit for use in clinical laboratories for the quantitative determination of the number of triplet repeats in the genes ATXN1 (SCA1), ATXN2 (SCA2), ATXN3 (SCA3), CACNA1A (SCA6), ATXN7 (SCA7), PPP2R2B (SCA12), TBP (SCA17) and ATN1 (DRPLA) genes, as an aid in the clinical diagnosis of autosomal dominant spinocerebellar ataxias.

The kit allows quantification of the size of healthy, intermediate, uncertain and expanded alleles with size equal to or less than 200 repeats. Expansions of more than 200 repeats described for SCA2 and SCA7 can be detected, but not quantified.

The procedure is based on the amplification of genomic DNA, extracted from whole blood and or buccal swab, by polymerase chain reaction (PCR or TP-PCR) with fluorescent primers, subsequent analysis of the size of the amplified fluorescent fragments in a capillary sequencer and conversion of the fragment size into the corresponding number of repeats.

The patient referred by the appropriate health specialist (e.g. neurologist), taking into account compatibility of presenting symptoms (autism spectrum disorder, delay in crawling, walking or rolling over, hyperactive or impulsive behaviour, intellectual disability, speech and language delay), and/or family history, may be subject to this determination. The intended user of this kit is technical personnel trained and qualified to perform the protocol described in the instructions for use and the interpretation of its results.

WORKFLOW:

RESULTS:

Limitations

• This kit can quantify all alleles up to 200 CAG repeats.
• Mutations (point mutations, insertions, deletions) at amplification primer sites are possible and may result in the lack of allele definition.
• Other technologies could be necessary to resolve the genotyping.
• Data and result interpretation should be revised by qualified personnel.