title: Verification of Inter-laboratorial Genotyping Consistency in the Molecular Diagnosis of Polyglutamine Spinocerebellar Ataxias.
abstract: 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.
authors.affiliation: Department of Biology/CIRN, University of the Azores, Rua da Mãe de Deus - Apartado 1422, 9501-801, Ponta Delgada, Azores, Portugal. amanda.ramos.reche@gmail.com.|Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal. amanda.ramos.reche@gmail.com.|Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal. amanda.ramos.reche@gmail.com.
authors.forename: Amanda
authors.initials: A
authors.lastname: Ramos
authors.affiliation: Department of Biology/CIRN, University of the Azores, Rua da Mãe de Deus - Apartado 1422, 9501-801, Ponta Delgada, Azores, Portugal.|Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Raposo
authors.affiliation: Department of Biochemistry and Molecular Genetics, Hospital Clínic and IDIBAPS, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Milà
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, England.
authors.forename: Conceição
authors.initials: C
authors.lastname: Bettencourt
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, England.
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
authors.affiliation: Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV-IPN), Mexico City, Mexico.
authors.forename: Bulmaro
authors.initials: B
authors.lastname: Cisneros
authors.affiliation: Laboratory of Genomic Medicine, Department of Genetics, National Rehabilitation Institute (INR), Mexico City, Mexico.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Magaña
authors.affiliation: Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.|Hospital de Santo Espírito da Ilha Terceira, SEEBMO, Angra do Heroísmo, Portugal.
authors.forename: Bruno Filipe
authors.initials: BF
authors.lastname: Bettencourt
authors.affiliation: Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.|Hospital de Santo Espírito da Ilha Terceira, SEEBMO, Angra do Heroísmo, Portugal.
authors.forename: Jácome
authors.initials: J
authors.lastname: Bruges-Armas
authors.affiliation: Unitat d'Antropologia Biològica, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Santos
authors.affiliation: Department of Biology/CIRN, University of the Azores, Rua da Mãe de Deus - Apartado 1422, 9501-801, Ponta Delgada, Azores, Portugal.|Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.
authors.forename: Manuela
authors.initials: M
authors.lastname: Lima
mesh_terms: D000067528:Ataxins / Q000235:genetics*; D005820:Genetic Testing / Q000592:standards*; D005838:Genotype; D060005:Genotyping Techniques / Q000592:standards*; D006801:Humans; D015588:Observer Variation; D010455:Peptides / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: D000067528:Ataxins; D010455:Peptides; C097188:polyglutamine
keywords: Fragment analysis; Molecular testing; Neurodegenerative disorders; SCA