title: Comparative multiplex dosage analysis in spinocerebellar ataxia type 2 patients.
abstract: We developed a new application of comparative multiplex dosage analysis (CMDA) for evaluation of the ataxin 2 gene. Expansions of the triplet CAG can cause spinocerebellar ataxia type 2 (SCA2), a neurodegenerative disease with an autosomal-dominant mode of inheritance. Molecular diagnosis of SCA2 is routinely based on the use of conventional PCR to detect the CAG expansion. However, PCR does not amplify an allele with an expansion of many triplets (>80), which is typically found in infantile and juvenile forms of SCA2, thus leading to false negatives. We propose the analysis of the ATXN2 gene by CMDA to complement existing methods currently used for the detection of large expansions of the CAG repeat. Using CMDA, the presence of any longer mutated allele in a heterozygous patient or fetus would be inferred due to dosage variation of the very frequent normal allele #22. CMDA can be completed in 1 day, at very low cost, and would be a useful tool for prenatal diagnosis and for diagnosis of presymptomatic forms of early-onset SCA2.
authors: Laboratory of Molecular Genetics, IRCCS Associazione Oasi Maria SS, Troina, Italy.
authors: F
authors: F
authors: Calì
authors: V
authors: V
authors: Chiavetta
authors: A
authors: A
authors: Ragalmuto
authors: M
authors: M
authors: Vinci
authors: G
authors: G
authors: Ruggeri
authors: P
authors: P
authors: Schinocca
authors: V
authors: V
authors: Romano
mesh_terms: D000483:Alleles; D000067528:Ataxins; D016022:Case-Control Studies; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D006801:Humans; D008297:Male; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000175:diagnosis / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion
chemical_list: D000067528:Ataxins; D009419:Nerve Tissue Proteins