Clinical phenotypes study of autosomal recessive cerebellar ataxia type 1 caused by SYNE 1 gene mutations / 中华神经科杂志

ABSTRACT

Objective To investigate the clinical features of autosomal recessive cerebellar ataxia type 1 (ARCA1) and analyze the pathogenic variants in SYNE 1 gene. Methods A cohort of 80 probands of autosomal recessive cerebellar ataxia pedigrees excluding Friedreich ataxia were detected by whole?exome sequencing technology. Potential pathogenic variants were confirmed by Sanger sequencing. Clinical phenotypes of positive patients were analyzed in detail. Results Three pedigrees of ARCA1 caused by SYNE 1 gene variants were found. The proband of pedigree 1 carried homozygous frameshift mutation c.12670dupC(p.L4224fs), presented as pure cerebellar ataxia. The proband of pedigree 2 carried compound heterozygous mutations c. 20826+1G>T and c. 25954C>T(p. R8652X), presented as cerebellar ataxia plus upper motor neuron dysfunction. The proband of pedigree 3 carried compound heterozygous mutations c.21955C>T(p.Q7319X) and c.23777C>A(p.T7926K), presented as mental behavior and cognitive impairment, cerebellar ataxia and upper motor neuron dysfunction. Brain MRI showed obvious cerebellar atrophy in all patients, and the fronto?temporal lobes were also found slight atrophy in proband of pedigree 3. Conclusions The phenotype of ARCA1 caused by SYNE 1 gene mutations is characterized by cerebellar ataxia, maybe accompanied with motor neuron damage and cognitive dysfunction. ARCA1 is a rare form of autosomal recessive cerebellar ataxia in Chinese population, with a complex phenotype. The use of next generation sequencing allows the rapid analysis of ARCA1, and will likely further expand genotype?phenotype correlations.