Duchenne肌营养不良家系临床表型及遗传学分析

Clinical phenotypes and genetic features of families with Duchenne muscular dystrophy

目的分析Duchenne肌营养不良(DMD)患儿家系临床表型与遗传学特点。方法选择基因检测明确诊断为DMD的7例患儿(6个家系)为研究对象,总结家系临床特征、遗传学特点。结果 6个家系中新发突变2个,母源遗传性4个。家系1先证者同时存在DMD基因1处点突变和1处插入突变,均为新发突变;3个家系为DMD基因点突变,1个家系为DMD基因外显子大片段缺失,1个家系DMD基因外显子大片段重复。所有先证者均具有骨骼肌运动障碍和肌酶改变,最小发病年龄为6个月,临床表型轻重不一;所有先证者心脏彩超检查结果均正常;3例先证者伴有轻度智力障碍。仅家系6先证者母亲具有轻度临床表型。结论基因检测可作为DMD确诊方法,智力障碍亦是DMD较多伴发的临床表型,早期心肌受累症状不显著,女性携带者可有轻度临床症状。

Objective To study the phenotypes and genetic features of families with Duchenne muscular dystrophy(DMD). Methods Seven children from six families with DMD diagnosed by gene testing were enrolled. The clinical and genetic features of the families were analyzed. Results There were two new mutations and four maternal inheritance mutations in the six families. The proband of family 1 had one point de novo mutation and one insertion de novo mutation of the DMD gene. Three families had point mutation, one family had fragment deletion of exon, and one family had fragment duplication of exon. The youngest age of onset of the probands was 6 months. All probands had skeletal muscle dyskinesia and significant changes in muscle enzymes, with different severities of clinical phenotypes. Three probands had mild mental retardation. The results of echocardiography were normal for all probands. The mother of the proband in family 6 had mild clinical phenotype. Conclusions Gene testing can be used for the confirmed diagnosis of DMD. Mental retardation is a frequent clinical phenotype of DMD. The symptoms of myocardial involvement are not obvious in the early stage. Female carriers may have mild clinical symptoms.