Genetic testing for ataxia in North America

Abstract

Background: The Ataxia Molecular Diagnostics Testing Group was established to generate quantitative proficiency and outcomes data regarding molecular testing for the autosomal dominant cerebellar ataxias (spinocerebellar ataxia types 1 [SCA-1] through -3, -6, and -7, and dentatorubral-pallidoluysian atrophy) in North America.

Methods and results: Twenty-four North American laboratories that offered diagnostic testing for one or more ataxia genes were initially identified through GeneTests (Children's Health Care System, Seattle, WA). Eighteen laboratories agreed to participate in the study, which consisted of completing a technical survey, clinical survey, and molecular proficiency test. One laboratory returned the completed surveys but did not perform the proficiency testing. Ten of 18 laboratories (56%) provided data on test volumes, and these laboratories collectively performed 2,240 tests; approximately 5% of the tests yielded a positive result (i.e., identification of a pathological trinucleotide (CAG) repeat expansion). In proficiency testing, 100% of the laboratories correctly genotyped all samples, and 93% of the laboratories were within 1 SD of the mean for sizing normal alleles (one repeat unit or less). Ninety percent of the laboratories were within 1 SD for sizing expanded alleles.

Conclusions: Proficiency testing showed little difference between laboratories with respect to allele sizing. However, additional phenotype/genotype correlations are necessary to define CAG repeat-length descriptors for SCA-1, SCA-2, and SCA-7 alleles of intermediate size.