A Second Case With the V374A Pathogenic Variant in an Italian Patient With Early-Onset Spinocerebellar Ataxia.

BACKGROUND AND OBJECTIVES

To date, approximately 20 heterozygous mainly loss-of-function variants in have been associated with spinocerebellar ataxia (SCA) type 19 and 22, a clinically heterogeneous group of neurodegenerative disorders. We aimed at reporting the second patients with the V374A mutation from an independent family, confirming its pathogenic role.

METHODS

We describe the clinical history of a patient with SCA and conducted genetic investigations including mitochondrial DNA analysis and exome sequencing.

RESULTS

This male patient was reported to have unstable gait with tremors at the lower limbs and dysarthric speech since childhood. A neurologic examination also showed dysarthria, nystagmus, action tremor, dysmetria, and weak deep tendon reflexes. He had marked cerebellar atrophy at brain MRI, more evident at vermis. Molecular analysis, including exome sequencing and an in silico panel analysis of genes associated with SCA, revealed the c.1121T>C [p.V374A] mutation in .

DISCUSSION

This report consolidates the pathogenicity of the V374A mutation and suggests that the ataxic paroxysmal exacerbations are not a key phenotypic feature of this mutation.