Duchenne型肌营养不良症的临床特点和基因分析

目的探讨Duchenne型肌营养不良症(DMD)的临床特点和基因特点,为临床诊断提供依据。方法回顾性分析2015—2019年中山大学附属第六医院遗传代谢实验室基因检测确诊的15例DMD患儿的基因检测结果和临床资料,探讨DMD的临床特征和基因特点。结果 15例患儿发病年龄1个月～12岁,临床表现以小腿腓肠肌假性肥大、Gowers征及走路摇摆(鸭步)为主,AST、ALT、CK、CK-MB及肌红蛋白等肌酶水平均明显升高。通过组合的高通量检测技术等检查DMD基因情况,结果多为缺失突变,共12例(80.0%),其中大片重复缺失突变10例(66.7%),点突变2例(13.3%);错义突变1例(6.6%);插入突变1例(6.6%);无义突变1例(6.6%)。其中7例(46.7%)患儿母亲进行了相关基因检测,4例患儿母亲为该基因突变点携带者。而根据ACMG变异类型,15例患儿中13例(86.7%)为致病突变,2例(13.3%)为疑似致病突变。同时15例病例中有2例暂无相关文献报道过。所有的突变可发生在基因的任何位置,但缺失的热点区域位于基因的中央区外显子45～55区共8例,占缺失突变的53.3%。结论...

Clinical characteristics and genotyping of Duchenne muscular dystrophy

Objective To explore the clinical and genetic characteristics of Duchenne muscular dystrophy(DMD),provide a basis for clinical diagnosis.Methods The genetic detection and clinical data of 15 children diagnosed as DMD after genetic detection in Laboratory of Genetics and Metabolism in the Sixth Hospital Affiliated to Sun Yat-sen University from 2015 to 2019 were analyzed retrospectively,the clinical and genetic characteristics of DMD were also analyzed.Results The age of onset in 15 children was from one month to 12 years,the main clinical manifestations included pseudohypertrophy of gastrocnemius muscle,Gowers sign,and waddling gait,the levels of AST,ALT,CK,CK-MB,and myohemoglobin increased significantly.High-throughput detection technology was used to detect genes of DMD children,deletion mutantion was the main type,accounting for 80.0%(12 cases),including 10 cases(66.7%)with wholesale duplication deletion mutation and 2 cases(13.3%)with point mutation;one case(6.6%)was diagnosed as missense mutation;one case(6.6%)was diagnosed as insertion mutation;one case(6.6%)was diagnosed as nonsense mutation.Seven mothers(46.7%)underwent related genetic detection,and four mothers were carriers.According to mutation types,13 cases(86.7%)were found with pathogenic mutations,2 cases(13.3%)were suspected of pathogenic mutations.Among 15 cases,2 cases were not reported by related literatures.The mutations could be found in any gene segment,but 8 cases were found with deletion of exon 45-55 regions of gene central region,accounting for 53.3%.Conclusion The main manifestations of DMD children include abnormal increases of liver function indexes and myocardial enzymes,and decrease of muscle force.Related genetic detection should be conducted among the children with abnormal increases of liver function indexes and myocardial enzymes.