A 24-year-old female presented with wasting and weakness of both hands and fasciculations over the chin for 12 years, followed by an imbalance while walking and speech changes after 10 years. Her 12-year-old sister also had a similar clinical presentation. There were fasciculations over the chin, tongue, hands, back, and thighs with wasting and weakness in the tongue, and C7, C8, and T1 segments in both upper limbs along with bipyramidal signs. There was limb and gait ataxia. Magnetic resonance imaging brain showed pan cerebellar 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 a frameshift and premature termination of the protein ‘Nesprin 1’. Amyotrophic lateral sclerosis-like presentation followed by cerebellar ataxia has been described with SYNE1 ataxia. This unique phenotype and novel deletion mutation of the SYNE1 gene is the first case reported from India.
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