Synaptic Nuclear Envelope Protein 1 (SYNE 1) Ataxia with Amyotrophic Lateral Sclerosis-like Presentation: A Novel...

A 24-year-old female presented with wasting and weakness of both hands and fasciculations over the chin since 12 years, followed by imbalance while walking and speech changes since 10 years. Her 12-year-old sister also had a similar clinical presentation. There were fasciculations over the chin, tongue, hands, back, thighs with wasting and weakness in tongue, and C7, C8, T1 segments in both upper limbs along with bipyramidal signs. There was limb and gait ataxia. Magnetic resonance imaging brain showed pancerebellar atrophy, and electromyography was suggestive of anterior horn cell involvement in bulbar, cervical, thoracic, and lumbar segments. Next-generation sequencing identified a novel likely pathogenic deletion mutation: chr6:152527389_152527399del, c.22711_22721del, and p.Ala7571ArgfsTer4 in exon 125 of synaptic nuclear envelope protein 1 (SYNE1) gene. This mutation leads to frameshift and premature termination of the protein 'Nesprin 1'. Amyotrophic lateral sclerosis-like presentation followed by cerebellar ataxia have been described with SYNE1 ataxia. This unique phenotype and novel deletion mutation of SYNE1 gene is the first case reported from India.