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This research focuses on the clinical manifestations and genetic basis of SCAR8 due to SYNE1 mutations.

March 19, 2026Open Access

Multisystemic Involvement in Autosomal Recessive Cerebellar Ataxia Type 8 Having a Novel SYNE1 Nonsense Variant

SHShoko HongoNiigata University TKTakuya KonnoUnitika (Japan)YHYuya Hatano

Key Points

This research focuses on the clinical manifestations and genetic basis of SCAR8 due to SYNE1 mutations.
Case analysis of a 33-year-old woman with SCAR8.
Performed whole-exome sequencing for genetic evaluation.
Conducted a literature review on SYNE1 variants and symptoms.
Identified compound heterozygous nonsense variants in SYNE1.
The novel variant c.18727C>T led to a 23% reduction in SYNE1 mRNA expression.
Multisystemic symptoms included motor neuron disease and respiratory dysfunction.

Abstract

Autosomal recessive cerebellar ataxia type 8 (SCAR8) is a neurodegenerative disorder caused by variants of the SYNE1 gene. It presents with progressive cerebellar ataxia, and some patients exhibit multisystemic symptoms. A 33-year-old woman had cerebellar ataxia since childhood, motor neuron disease, vocal cord abduction paralysis, joint deformities, oculocutaneous telangiectasia, and obesity, and required a tracheostomy. Whole-exome sequencing revealed compound heterozygous nonsense variants of SYNE1 (NM₀33071. 5), including the novel variant c. 18727C>T (p. Gln6243Ter). The SYNE1 mRNA expression was reduced by 23% relative to that in the controls. A literature review, including this case, revealed that SYNE1 variants tend to cluster in the C-terminal region in patients with respiratory dysfunction.

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