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.


中文翻译：

---

突触性核膜蛋白1（SYNE 1）共济失调伴肌萎缩性侧索硬化样表现：来自印度的新型突触核膜蛋白1（SYNE 1）基因缺失突变。


一名24岁女性自12年以来表现出下巴的虚弱，双手无力和束缚，随后10年以来行走和言语变化不平衡。她的12岁姐姐也有类似的临床表现。下巴，舌头，手，背部，大腿上有束缚，舌头虚弱无力，两个上肢的C7，C8，T1段以及双锥体信号征。有肢体和步态共济失调。脑部磁共振成像显示前脑萎缩，肌电图提示前角细胞累及延髓，宫颈，胸廓和腰椎节段。下一代测序在突触核被膜蛋白1（125）的外显子125中鉴定了一个新的可能的病原性缺失突变：chr6：152527389_152527399del，c.22711_22721del和p.Ala7571ArgfsTer4（SYNE1）基因。这种突变导致蛋白“ Nesprin 1”移码并过早终止。SYNE1共济失调描述了肌萎缩性侧索硬化样表现，然后是小脑共济失调。SYNE1基因的这种独特的表型和新的缺失突变是印度报道的第一例。