Clinical analysis and literature review of sporadic amyotrophic lateral sclerosis caused by a novel mutation of MATR3 gene / 中华神经科杂志

ABSTRACT

Objective:To analyze the clinical data and related literature of sporadic amyotrophic lateral sclerosis (sALS) caused by a new mutation of MATR3 gene.Methods:A sALS patient with MATR3 gene mutation who was admitted to the Department of Neurology, the First Medical Center of Chinese People′s Liberation Army General Hospital was collected. The examination of biochemistry, electromyography, cranial magnetic resonance imaging (MRI) and genetic tests, etc, were performed. Whole exon sequencing was performed to screen the disease-causing genes. Sanger sequencing was also performed to validate the mutation sites of the patient. Genetic harmfulness was predicted by multiple computational softwares, including SIFT Pred, Polyphen-2 HVAR Pred and MutationTaster Pred. Clinical characteristics of ALS induced by different MATR3 gene mutation sites were summarized by database retrieval.Results:The patient was a 69-year-old female, who began to show bulbar muscle weakness and then gradually developed to the facial muscles, including temporalis and masseter, and four limbs. In addition to the upper and lower motor neuron damage found in physical examination of the patient, the obvious facial muscle atrophy was also found in the patient. There was no family history of ALS in this patient. In terms of auxiliary examination, creatine kinase, rheumatism immunity and tumor markers were all normal. Cranial MRI showed no structural lesions and abnormal signals at the course of pyramidal tract. Electromyography suggested extensive neurogenic damage, decreased amplitude of repeated stimulation, abnormal measurement of blink reflex (BR) and skin sympathetic response (SSR). A heterozygous variant c.1472A>G (p.Y491C) of the MATR3 gene, which is a missense mutation, was detected in the patient. The variant was predicted as a harmful mutation by multiple computational softwares.Conclusions:A variant c.1472A>G (p.Y491C) of the MATR3 gene may be the pathogenic mutation of the patient. The patient not only has similar clinical manifestations to those of classic ALS, but also has facial muscle involvement. The electromyography shows abnormal SSR and BR.