一例MSTO1基因复合杂合变异所致的线粒体肌病并小脑萎缩共济失调患儿的分析

Diagnosis of a child with mitochondrial myopathy and cerebellar atrophy with ataxia due to compound heterozygous variants of MSTO1 gene

目的分析1例表现肌病和小脑萎缩共济失调患儿的遗传学病因。方法对患儿进行临床和实验室检查,应用全外显子二代测序技术对患儿进行检测,对可疑变异位点进行致病性预测,并进行患儿及其父母的Sanger测序验证。结果患儿表现为运动发育落后、共济失调、肌张力减低,血清肌酸激酶升高,头部磁共振成像显示小脑萎缩且进行性加重。基因检测示患儿MSTO1基因c.13delG(p.Ala5ProfsTer68)和c.971C>T(p.Thr324Ile),分别来源于母亲和父亲,前者移码变异尚未见报道,依据美国医学遗传学与基因组学学会指南判断其为可能致病;后者错义变异已有报道,依据指南判断为意义未明。结论MSTO1基因c.13delG(p.Ala5ProfsTer68)和c.971C>T(p.Thr324Ile)复合杂合变异丰富了MSTO1基因的变异数据库,该基因复合杂合变异引起线粒体肌病并小脑萎缩共济失调,可能导致患儿发病。

Objective To explore the genetic basis for a child with myopathy and cerebellar atrophy with ataxia.Methods Clinical examinations and laboratory testing were carried out for the patient.The proband and the parents’genomic DNA was extracted from peripheral blood samples and subjected to trio whole-exome sequencing.Candidate variant was validated by Sanger sequencing.Results The 1-year-and-8-month-old boy manifested motor developmental delay,ataxia,hypomyotonia,increased serum creatine kinase.Cranial MRI showed cerebellar atrophy with progressive aggravation.Genetic testing revealed that the patient has harbored compound heterozygous variants of the MSTO1 gene,namely c.13delG(p.Ala5ProfsTer68)and c.971C>T(p.Thr324Ile),which were respectively inherited from his mother and father.The former was unreported previously and was predicted to be likely pathogenic,whilst the latter has been reported previously and was predicted to be of uncertain significance.Conclusion The compound heterozygous c.13delG(p.Ala5ProfsTer68)and c.971C>T(p.Thr324Ile)variants probably underlay the disease in the proband.Above finding has enriched the spectrum of MSTO1 gene variants underlying mitochondrial myopathy and cerebellar atrophy with ataxia.