Verification of Inter-laboratorial Genotyping Consistency in the Molecular Diagnosis of Polyglutamine Spinocerebellar Ataxias

• DOI: 10.1007/s12031-015-0646-y
• Publication Date: 2015-10-10T06:17:28Z
• Authors: Amanda Ramos; Mafalda Raposo; Montserrat Milà; Conceição Bettenc...; Henry Houlden; Bulmaro Cisneros; Jonathan J. Magaña; Bruno Filipe Bett...; Jácome Bruges-Armas; Cristina Santos; Manuela Lima
• Keywords: Observer Variation; 0301 basic medicine; 0303 health sciences; Genotype; Genotyping Techniques; 7. Clean energy; 3. Good health; 03 medical and health sciences; Ataxins; 13. Climate action; Humans; Spinocerebellar Ataxias; Genetic Testing; Peptides; Trinucleotide Repeat Expansion

The polyglutamine spinocerebellar ataxias (SCAs) constitute a clinically and genetically heterogeneous group of rare late-onset neurodegenerative disorders, caused by CAG expansions in the coding region of the respective genes. Given their considerable clinical overlapping, differential diagnosis relies on molecular testing. Laboratory best practice guidelines for molecular genetic testing of the SCAs were released in 2010 by the European Molecular Genetics Quality Network, following the recognition of gross genotyping errors by some diagnostic laboratories. The main goal of this study was to verify the existence of inter-laboratorial consistency comparing genotypes for SCA1, SCA2, SCA3, SCA6 and SCA7 obtained by independent diagnostic laboratories. The individual impact of different methodological issues on the genotype for the several SCAs was also analysed. Four international collaborative diagnostic laboratories provided 79 samples and the respective SCA genotypes. Samples were genotyped in-house for all SCAs using an independent methodology; comparison of the allele size obtained with the one provided by the collaborative laboratories was performed. Globally, no significant differences were identified, a result which could be reflecting the fulfilment of recommendations for the molecular testing of SCAs and demonstrating an improvement in genotyping accuracy.