M Arias1, M García-Murias2, M J Sobrido2. 1. Servicio de Neurología, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, España. Electronic address: manuel.arias@usc.es. 2. Grupo de Neurogenética del Instituto de Investigación Sanitaria (IDIS), Centro de Investigación Biomédica en red de Enfermedades Raras (CIBERER), Santiago de Compostela, España.
Abstract
INTRODUCTION- OBJECTIVE: To describe the history of the discovery of SCA36 and review knowledge of this entity, which is currently the most prevalent hereditary ataxia in Galicia (Spain) owing to a founder effect. DEVELOPMENT: SCA36 is an autosomal dominant hereditary ataxia with late onset and slow progression. It presents with cerebellar ataxia, sensorineural hearing loss, and discrete motor neuron impairment (tongue atrophy with denervation, discrete pyramidal signs). SCA36 was first described in Japan (Asida River ataxia) and in Galicia(Costa da Morte ataxia). The condition is caused by a genetic mutation (intronic hexanucleotide repeat expansion) in the NOP56 gene on the short arm of chromosome 20 (20p13). Magnetic resonance image study initially shows cerebellar vermian atrophy that subsequently extends to the rest of the cerebellum and finally to the pontomedullary region of the brainstem without producing white matter lesions. Peripheral nerve conduction velocities are normal, and sensorimotor evoked potential studies show delayed conduction of stimuli to lower limbs. In patients with hearing loss, audiometric studies show a drop of >40dB in frequencies exceeding 2,500Hz. Auditory evoked potential studies may also show lack of waves I and II. CONCLUSIONS: Costa da Morte ataxia or SCA36 is the most prevalent SCA in the Spanish region of Galicia. Given the region's history of high rates of emigration, new cases may be diagnosed in numerous countries, especially in Latin America. Genetic studies are now available to patients and asymptomatic carriers. Since many people are at risk for this disease, we will continue our investigations aimed at elucidating the underlying pathogenic molecular mechanisms and discovering effective treatment.
INTRODUCTION- OBJECTIVE: To describe the history of the discovery of SCA36 and review knowledge of this entity, which is currently the most prevalent hereditary ataxia in Galicia (Spain) owing to a founder effect. DEVELOPMENT: SCA36 is an autosomal dominant hereditary ataxia with late onset and slow progression. It presents with cerebellar ataxia, sensorineural hearing loss, and discrete motor neuron impairment (tongue atrophy with denervation, discrete pyramidal signs). SCA36 was first described in Japan (Asida River ataxia) and in Galicia(Costa da Morte ataxia). The condition is caused by a genetic mutation (intronic hexanucleotide repeat expansion) in the NOP56 gene on the short arm of chromosome 20 (20p13). Magnetic resonance image study initially shows cerebellar vermian atrophy that subsequently extends to the rest of the cerebellum and finally to the pontomedullary region of the brainstem without producing white matter lesions. Peripheral nerve conduction velocities are normal, and sensorimotor evoked potential studies show delayed conduction of stimuli to lower limbs. In patients with hearing loss, audiometric studies show a drop of >40dB in frequencies exceeding 2,500Hz. Auditory evoked potential studies may also show lack of waves I and II. CONCLUSIONS: Costa da Morte ataxia or SCA36 is the most prevalent SCA in the Spanish region of Galicia. Given the region's history of high rates of emigration, new cases may be diagnosed in numerous countries, especially in Latin America. Genetic studies are now available to patients and asymptomatic carriers. Since many people are at risk for this disease, we will continue our investigations aimed at elucidating the underlying pathogenic molecular mechanisms and discovering effective treatment.
Keywords:
Ataxia da Costa da Morte; Ataxia espinocerebelosa tipo 36; Costa da Morte ataxia; Expansión de hexanucleótido; Hereditary ataxias; Heredoataxias; Hexanucleotide expansion; NOP56; Spinocerebellar ataxia type 36
Authors: Zachary T McEachin; Tania F Gendron; Nisha Raj; María García-Murias; Anwesha Banerjee; Ryan H Purcell; Patricia J Ward; Tiffany W Todd; Megan E Merritt-Garza; Karen Jansen-West; Chadwick M Hales; Tania García-Sobrino; Beatriz Quintáns; Christopher J Holler; Georgia Taylor; Beatriz San Millán; Susana Teijeira; Toru Yamashita; Ryuichi Ohkubo; Nicholas M Boulis; Chongchong Xu; Zhexing Wen; Nathalie Streichenberger; Brent L Fogel; Thomas Kukar; Koji Abe; Dennis W Dickson; Manuel Arias; Jonathan D Glass; Jie Jiang; Malú G Tansey; María-Jesús Sobrido; Leonard Petrucelli; Wilfried Rossoll; Gary J Bassell Journal: Neuron Date: 2020-05-05 Impact factor: 17.173