Nallapaneni Lakshmi Madhuri, Mehta Anish, Hiremath Prabhudev, Pradeep R, Javali Mahendra, Acharya Purushotham T
Department of Neurology, Ramaiah Medical College and Hospitals, Ramaiah University of Applied Sciences, Bengaluru, India.
Cerebellum. 2024 Dec 27;24(1):19. doi: 10.1007/s12311-024-01779-7.
Spinocerebellar ataxias (SCAs) are a diverse and heterogeneous group of inherited neurodegenerative disorders marked by progressive ataxia and cerebellar degeneration. This case report details an 11-year-old Indian boy with childhood-onset ataxia and severe sensorineural hearing loss, a rarely reported concomitance in pediatric neurology. Genetic analysis identified a unique heterozygous 3' splice site variant in the PNPT1 gene (c.2014-3 C > G) of pathogenic significance, confirming the diagnosis of SCA25. This case highlights the phenotypic and genotypic heterogeneity of PNPT1 gene-related SCA25 and suggests an autosomal dominant inheritance pattern with low penetrance. It underscores the need for functional studies to further validate the splice variant reported herein and emphasizes the importance of a high index of suspicion for genetic analysis and genetic counselling in children with concurrent hearing loss and progressive ataxia, even in the absence of a clear autosomal dominant inheritance pattern.
脊髓小脑共济失调（SCAs）是一组多样且异质性的遗传性神经退行性疾病，其特征为进行性共济失调和小脑变性。本病例报告详细介绍了一名11岁的印度男孩，他患有儿童期起病的共济失调和严重的感音神经性听力损失，这在儿科神经病学中是鲜有报道的并存情况。基因分析在PNPT1基因中鉴定出一个具有致病意义的独特杂合3'剪接位点变异（c.2014-3 C＞G），确诊为SCA25。本病例突出了PNPT1基因相关SCA25的表型和基因型异质性，并提示其为常染色体显性低外显率遗传模式。它强调需要进行功能研究以进一步验证本文报道的剪接变异，并强调对于同时患有听力损失和进行性共济失调的儿童，即使没有明确的常染色体显性遗传模式，也需高度怀疑并进行基因分析和遗传咨询。
