一个假肥大型肌营养不良症伴心脏扩大家系的遗传学及临床研究  

Genetic and clinical study on a family with Becker's muscular dystrophy combined with cardiac dilatation

作　　者：刘亚欣[1] 高凌根[2] 周宪梁[1] 宋雷[1] 王林平[1] 张琳[1] 田涛[1] 孙凯[1] 王继征[1] 邹玉宝[1] 蒋雄京[1] 张慧敏[1] 吴海英[1] 郑德裕[1] 惠汝太 

机构地区：[1]北京协和医学院,中国医学科学院国家心脏病中心阜外心血管医院高血压诊治中心,北京1100037 [2]解放军总医院南楼临床部心血管一科,北京2100853

出　　处：《中国分子心脏病学杂志》2012年第6期325-328,共4页Molecular Cardiology of China

基　　金：中国医学科学院北京协和医学院2011年中央级公益性科研院所基本科研业务费

摘　　要：背景假肥大型进行性肌营养不良是由抗肌萎缩蛋白基因突所致的一种X连锁隐性遗传神经肌肉疾病,又称为杜氏或贝克肌营养不良(Duchenne’s or Becker’s muscular dystrophy;DMD or BMD),是以缓慢进行性加重的对称性肌无力和肌萎缩为特点的遗传性肌肉病变,其中DMD病情严重,预后差;BMD病情进展相对缓慢,可累及心脏。目的总结假肥大型肌营养不良症伴心脏扩大患者的临床特征并进行基因分析和系统治疗,为临床诊治提供借鉴。方法:对先证者和家系成员进行临床观察、血清酶、肌电图、心电图、心脏彩色超声检查及心脏核磁检查,采用直接测序的方法进行抗肌萎缩蛋白基因突变的检测,尚需对100例无血缘关系的健康人群进行该位点的基因扩增测序,以排除所发现的突变为未知人群多态位点的可能。对确诊患者根据病情进行对症治疗并对其进行随访。结果先证者符合BMD诊断,基因检测结果提示先证者携带dystrophin基因突变(c.4998_5000DelGCA,p.1667del)。家系成员中检测出3例患者携带以上突变,携带者均表现为四肢近端肌肉萎缩、无力,双腓肠肌假性肥大,血清肌酶水平显著增高,心脏受累,先证者接受心脏移植术,恢复良好。结论本研究通过基因检测为先证者明确诊断,并对家系成员进行基因筛查,心脏移植术是治疗BMD晚期患者的可行有效的方法。Background Duchenne＇s or Becker＇s muscular dystrophy is a serious X- linked neuromuscular disorder. Mutations in the dystro- phin gene on chromosome Xp21.1. have been reported to cause BMD. It primarily involved the skeletal muscle, characterized by weakness and mus- cle atrophy of hereditary muscle disease following as low progressive increase of symme try. DMD is usually with serious condition and with a poor prognosis. BMD patients can usually walk and have a near normal life span, and there is a chance of them developing cardiac problems. Objective： To study the clinical characteristics and genetic analysis and management of Becket＇s muscular dystrophy combined with cardiac involvement, and to expand our understanding of this disorder. Methods The proband and the family members had genetic testing, and these subjects also had physi- cal examination and received muscle biopsy and routine pathological checks and cardiac evaluation. One hundred control subjects without diagnostic features of B MD were also recruited. Genomic DNA was extracted from leukocytes of peripheral blood from the patients and the control subjects. We screened the dystrophin gene in the indexes, and also screened for the mutation in their families and 100 controls. Results The proband was diagnosed with BMD by the identification of a mutation（ c.4998_5000Del GCA,p. 1667del） in the exon 35 of the dystrophin gene. Three cases were diagnosed with BMD by the identification of this mutation. All genetically affected subjects had a history of weakness of the quadriceps femoris as well as increased serum creatine kinase level at rest and cardiac involvement. Conclusion Genetic analysis enables a precise diagnosis of BMD, and heart transplantation is an effective treatment for the patient with severe heart failure.

关 键 词：贝克肌营养不良 心脏损害 基因分析 心脏移植 

分 类 号：R746.2[医药卫生—神经病学与精神病学]