ASAH1 gene mutation causing spinal muscular atrophy with progressive myoclonic epilepsy in a Chinese child and literature review / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate the clinical and genetic features of a Chinese child with spinal muscular atrophy with progressive myoclonic epilepsy(SMA-PME)and review the related literatures.Methods The clinical and genetic data of 1 patient with SMA-PME,who had visited the Department of Pediatrics,Peking University First Hospital in August 2016,were analyzed.The clinical and genetic features of 10 reported ASAH1-related cases and this case were reviewed.Results The patient was a girl aged 4 years.At the age of 1 year and 2 months,she was able to walk independently and then started to show slowly progressive difficulty in walking.At age 3 years and 9 months,she developed frequent myoclonic jerks of trunk or even falls,and had occasional staring.The patient was revealed to have compound heterozygous mutations in ASAH1 gene,c.256_c.257insA(p.T86Nfs*14)inherited from her father and c.125C>T(p.T42M)inherited from her mother.The mutation p.T86Nfs*14 was not reported before.Since the onset of the disease,her motor skills were progressive impaired but intelligence was basically normal.A total of 10 ASAH1-related cases were reported until October 2016.By analyzing the data of the 10 foreign cases and this case,muscular weakness and seizures were presented in all cases.Onset usually with muscular weakness,other symptoms including tremor,dysphagia and recurrent pneumonia etc.The total 8 mutations were found and the most frequent mutation was c.125C>T.The mode of inheritance all conformed to autosomal recessive.In all cases,early developmental milestones were normal,and no obvious cognitive impairment were found during the course of the disease in some of them.Four ca-ses were dead at the age of 13 to 19 years in the literatures.Conclusion SMA-PME is a rare autosomal recessive disease associated with mutations of ASAH1 gene.The patient is the first Chinese case of SMA -PME confirmed by ASAH1 gene mutations that including a common mutation and a novel frame shift mutation.