NGS-based detection of a novel mutation in PRKCG (SCA14) in sporadic adult-onset ataxia plus dystonic tremor

Excerpt

Degenerative ataxias are a group of rare neurodegenerative diseases (mean prevalence of 2.7/100,000) including both inherited and sporadic forms, which are characterized by wide clinical and genetic heterogeneity, with more than 150 distinct genetic loci so far associated with such phenotype. The autosomal dominant spinocerebellar ataxias (AD-SCAs) are the most frequent genetic subtypes, mostly due to polyglutamine encoding and CAG repeat expansions. Non-coding repeat expansions and conventional mutations together account for about 10% of cases, while the remaining 30–40% of patients, depending on various cohorts, remain undiagnosed [1]. Because of such genetic heterogeneity, next-generation sequencing (NGS) techniques are representing an important tool in the diagnostic setting of inherited degenerative ataxias, allowing rapid and cost-effective genetic screening, able to increase the diagnostic yield in such disorders, even in apparently sporadic cases, and also to expand the mutational spectrum of specific genes [2]. …