Discovery and characterisation of spinocerebellar ataxia type 36 or “Costa da Morte ataxia”

M. Arias
Neurosciences and History 2020;8(3):99-108

Type of article: REVIEW

AUTHOR

M. Arias
Neurology Department. Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.

ABSTRACT

This study presents a chronological account of how and when a variety of degenerative ataxia was identified in Costa da Morte (a region on the Atlantic coast of Galicia, Spain); the disease was named spinocerebellar ataxia type 36 (SCA36) following the discovery of the causal genetic mutation, and it now represents the most prevalent autosomal dominant hereditary ataxia in Galicia. The same disease was described in the region of the river Asida (Chugoku, Japan) early in the second decade of the 21st century, with no knowledge or relationship between the two groups.
Patients present imbalance, usually slowly progressive and with onset in the fifth decade of life; other clinical features include hearing loss and dysarthria with atrophy and fasciculations of the tongue. Some patients present a discrete cognitive and affective cerebellar syndrome, which may precede motor symptoms.
Structural neuroimaging shows atrophy of the vermis, extending to the rest of the cerebellum and brainstem; ¹⁸F-FDG PET has detected hypometabolism in the right cerebellar hemisphere in preataxic patients.
SCA36 is caused by a (TG₃C₂)_n hexanucleotide expansion in intron 1 of the NOP56 gene, resulting in intranuclear inclusions (RNA foci) and aberrant synthesis of dipeptides, which cause neuronal dysfunction, and particularly the loss of Purkinje cells. SCA36 and C9orf72 mutations (the main cause of amyotrophic lateral sclerosis and frontotemporal dementia) are caused by hexanucleotide expansions, a peculiarity that has led to several concomitant research projects studying both entities: the elimination or silencing of these expansions by gene therapy may enable us to slow or cure both conditions.

KEYWORDS

CA36, NOP56, MRI, PET, cerebellum

Neurosciences and History 2020;8(3):99-108