Objective: To investigate genetic causes of cerebellar ataxia in Korea using whole exome sequencing (WES)

Background: Cerebellar ataxia encompasses a number of neurological conditions with diverse etiologies ranging from acquired to genetic disorders. Molecular diagnosis of genetic ataxia is challenging because heterogeneous phenotypes often make it difficult to set the priority of test methods and to perform genotype-phenotype correlation. Previous studies on genetic ataxias were performed on Caucasians. In this study, we explored the contribution of genetic disorders in patients with undiagnosed ataxia in Korea.

Method: Patients with cerebellar ataxia who visited the movement disorder clinic from March 2014 to December 2018 were screened. Excluding acquired, degenerative and trinucleotide repeat ataxias such as spinocerebellar ataxia 1 (SCA1), SCA2, SCA3, SCA6, SCA7, SCA8, SCA17, dentatorubral-pallidoluysian atrophy and Friedreich ataxia, 77 patients from 68 families were enrolled. WES and phenotypic correlations were performed.

Results: Overall, 18 families had pathogenic or likely pathogenic variants in 14 different genes, including NEU1, APTX, SPG7, HTRA1, POLG2, SYNE1, CACNA1G, CACNA1A, ITPR1, AHI1, SPG11, ANO10, ATM, and C5orf42, resulting in a diagnostic yield of 26.5%. Variants of unknown significance were found in 15 (22.1%) families, 8 of whom were clinically compatible with the genetic diagnosis, increasing the diagnostic yield to 38.2%.

Conclusion: Using WES, this study provided definitive and potential diagnoses for Korean patients with undiagnosed ataxia. Our study has clinical implication for neurology practice, providing diagnosis of ataxia and phenotypic expansion of genetic variants.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/whole-exome-sequencing-in-patients-with-undiagnosed-ataxia-in-a-korean-population/