POMT1和POMT2基因突变导致的2例α-抗肌萎缩相关糖蛋白病

POMT1 and POMT2 gene mutations result in 2 cases of alpha-dystroglycanopathy

抗肌萎缩相关糖蛋白病(alpha-dystroglycanopathy,α-DGP)是由于α-抗肌萎缩相关糖蛋白(alphadystroglycan,α-DG)异常糖基化导致的一组先天性肌营养不良症和肢带型肌营养不良症,国内目前对于该类疾病的临床表现、遗传学特点及诊断方法研究较少。中南大学湘雅医院儿科收治2例由O-甘露糖转移酶(protein Omannosyltransferases,PMTs)家族的POMT1、POMT2基因突变导致的α-DGP患者。2例患者均表现为运动落后,伴或不伴有智力损害,血清肌酸激酶(creatine kinase,CK)水平显著升高,肌电图检查结果提示肌源性损害,肌肉活检符合肌病表现。遗传学检测发现2例患者均有复合杂合突变,2例患者的父母均为携带其中一种突变的杂合子;1例患者为POMT1基因c.824+1G>A,splicing和c.1777G>A,p.A593T,另1例患者为POMT2基因c.604T>G,p.F202V和c.868C>T,p.P290S。利用在线数据库进行预测,结果提示突变位点具有致病性。2例患者分别确诊为先天性肌营养不良伴智力障碍(congenital muscular dystrophy with mental retardation,CMD-MR)及肢带型肌营养不良2N型(limbgirdle muscular dystrophytype 2N,LGMD2N)。PMTs家族有着相似的序列,基因突变均可导致不同程度的肌营养不良,且伴随血清CK水平的升高。α-DGP很容易误诊,遗传学检查有益于早期诊断、预后判断及遗传咨询。

Alpha-dystroglycanopathy(α-DGP)is a group of congenital muscular dystrophy and limb band muscular dystrophy caused by abnormal glycosylation ofα-dystroglycan(α-DG).At present,there are few studies on the clinical manifestations,genetic characteristics,and diagnostic methods forα-DGP in China.Two cases ofα-DGP caused by POMT1 and POMT2 gene mutations in the protein O-mannosyltransferases(PMTs)family were admitted to the Department of Pediatrics,Xiangya Hospital,Central South University.The 2 patients showed exercise retardation,with or without mental retardation.Serum level of creatine kinase(CK)was increased significantly.Electromyography showed myogenic impairment.Muscle biopsy was consistent with myopathy.Genetic test showed that both patients had compound heterozygous mutations,and the parents of the 2 patients were heterozygous with one of the mutations.There were c.824+1G>A,splicing and c.1777G>A,p.A593T in POMT1 gene,and c.604T>G,p.F202V and c.868C>T,p.P290S in POMT2 gene.The online database was used to predict the mutation sites and suggested the pathogenicity.Finally,one patient was diagnosed as congenital muscular dystrophy with mental retardation(CMD-MR)and the other was dystrophytype 2 N(LGMD2N).PMTs family has similar sequences.Gene mutations can lead to different degrees of muscular dystrophy with the increase of serum level of CK.α-DG is easy to be misdiagnosed.Genetic examination is beneficial to early diagnosis,prognosis,and genetic counseling.