Autosomal recessive spinocerebellar ataxia SCAR8/ARCA1: First families detected in Spain

Autores de IDIVAL

• 

  Marta Fernández Matarrubia

  Autor

Autores ajenos al IDIVAL

• Arias, M
• Mir, P
• Arpa, J
• Garcia-Ramos, R
• Blanco-Arias, P
• Quintans, B
• Sobrido, MJ

Unidades

• ENFERMEDADES NEURODEGENERATIVAS

  

  Investigador Responsable

  Jon Infante Ceberio

Abstract

Introduction: Autosomal recessive spinocerebellar ataxia type 8 (ARCA1/SCAR8) is caused by mutations of the SYNE1 gene. The disease was initially described in families from Quebec (Canada) with a phenotype of pure cerebellar syndrome, but in recent years has been reported with a more variable clinical phenotype in other countries. Cases have recently been described of muscular dystrophy, arthrogryposis, and cardiomyopathy due to SYNE1 mutations. Objective: To describe clinical and molecular findings from 4 patients (3 men and one woman) diagnosed with ARCA1/SCAR8 from 3 Spanish families from different regions. Material and methods: We describe the clinical, paraclinical, and genetic results from 4 patients diagnosed with ARCA1/SCAR8 at different Spanish neurology departments. Results: Onset occurred in the third or fourth decade of live in all patients. After 15 years of progression, 3 patients presented pure cerebellar syndrome, similar to the Canadian patients; the fourth patient, with over 30 years' progression, presented vertical gaze palsy, pyrami-dal signs, and moderate cognitive impairment. In all patients, MRI studies showed cerebellar atrophy. The genetic study revealed distinct pathogenic SYNE1 mutations in each family. Conclusions: ARCA1/SCAR8 can be found worldwide and may be caused by many distinct muta-tions in the SYNE1 gene. The disease may manifest with a complex phenotype of varying severity. (c) 2019 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U. All rights reserved.

Keywords

• Ataxia; Autosomal recessive inheritance; SYNE1; ARCA1; SCAR8; Sequencing; Gene panel