Introduction: Mutations in the PUM1 gene were recently identified to cause spinocerebellar ataxia type 47 (SCA47). However, their role in cerebellar ataxia in various populations remains elusive. The aim of this study was to elucidate the frequency and spectrum of PUM1 mutations in a cohort of Taiwanese patients with molecularly undetermined cerebellar ataxia.
Methods: Mutational analyses of PUM1 were performed by Sanger sequencing in a cohort of 248 unrelated patients with cerebellar ataxia of unknown cause, including 108 with autosomal-dominantly inherited cerebellar ataxia, 45 with autosomal-recessively inherited cerebellar ataxia, and 95 with apparently sporadic cerebellar ataxia. Among them, the genetic causes of ataxia remained unknown after excluding mutations responsible for SCA1, 2, 3, 6, 7, 8, 10, 12, 17, 19/22, 23, 26, 27, 28, 31, 35, 36, dentatorubral-pallidoluysian atrophy and Friedreich's ataxia.
Results: Two heterozygous missense PUM1 variants were identified in two patients with apparently sporadic cerebellar ataxia, including a known disease-causing mutation (p.R1139W) and a variant of uncertain significance (p.K151R). The patient carrying the p.R1139W mutation had a slowly progressive, relatively pure cerebellar ataxia, presenting with gait unsteadiness, limb dysmetria, ataxic dysarthria and saccadic pursuit.
Conclusion: Our findings support the pathogenic role of PUM1 mutations in cerebellar ataxia and emphasize the importance of considering PUM1 mutations as a possible etiology of cerebellar ataxia.
Keywords: Cerebellar ataxia; PUM1; Pumilio1; SCA47; Spinocerebellar ataxia.
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