R25G mutation in exon 1 of LMNA gene is associated with dilated cardiomyopathy and limb-girdle muscular dystrophy 1B  

作　　者：YUAN Wo-liang HUANG Chun-yan WANG Jing-feng XIE Shuang-lun NIE Ru-qiong LIU Ying-mei LIU Pin-ming ZHOU Shu-xian CHEN Su-qin HUANG Wei-jun 

机构地区：[1]Department of Cardiovascular Medicine, Second AffiliatedHospital of Sun Yat-sen University, Guangzhou, Guangdong510120, China [2]Department of Genetics, Sun Yat-sen University, Guangzhou,Guangdong 510089, China

出　　处：《Chinese Medical Journal》2009年第23期2840-2845,共6页中华医学杂志（英文版）

基　　金：This study was supported by the grant from Natural Science Foundation of Guangdong Province, China, 2005 （No. 5001673）.

摘　　要：Background Mutations of the LMNA gene encoding lamin A and C are associated with dilated cardiomyopathy （DCM）, conduction system defects and skeletal muscle dystrophy. Here we report a family with a mutation of the LMNA gene to identify the relationship between genotype and phenotype. Methods All 30 members of the family underwent clinical and genetic evaluation. A mutation analysis of the LMNA gene was performed. All of the 12 exons of LMNA gene were extended with polymerase chain reaction （PCR） and the PCR products were screened for gene mutation by direct sequencing. Results Ten members of the family had limb-girdle muscular dystrophy （LGMD） and 6 are still alive. Two patients suffered from DCM. Cardiac arrhythmias included atrioventricular block and atrial fibrillation; sudden death occurred in 2 patients. The pattern of inheritance was autosomal dominant. Mutation c.73C〉G （R25G） in exon 1 encoding the globular domains was confirmed in all of the affected members, resulting in the conversion of arginine （Arg） to glycine （Gly）. Conclusions The mutation R25G in exon 1 of LMNA gene we reported here in a Chinese family had a phenotype of malignant arrhythmia and mild LGMD, suggesting that patients with familial DCM, conduction system defects and skeletal muscle dystrophy should be screened by genetic testing for the LMNA gene.Background Mutations of the LMNA gene encoding lamin A and C are associated with dilated cardiomyopathy （DCM）, conduction system defects and skeletal muscle dystrophy. Here we report a family with a mutation of the LMNA gene to identify the relationship between genotype and phenotype. Methods All 30 members of the family underwent clinical and genetic evaluation. A mutation analysis of the LMNA gene was performed. All of the 12 exons of LMNA gene were extended with polymerase chain reaction （PCR） and the PCR products were screened for gene mutation by direct sequencing. Results Ten members of the family had limb-girdle muscular dystrophy （LGMD） and 6 are still alive. Two patients suffered from DCM. Cardiac arrhythmias included atrioventricular block and atrial fibrillation; sudden death occurred in 2 patients. The pattern of inheritance was autosomal dominant. Mutation c.73C〉G （R25G） in exon 1 encoding the globular domains was confirmed in all of the affected members, resulting in the conversion of arginine （Arg） to glycine （Gly）. Conclusions The mutation R25G in exon 1 of LMNA gene we reported here in a Chinese family had a phenotype of malignant arrhythmia and mild LGMD, suggesting that patients with familial DCM, conduction system defects and skeletal muscle dystrophy should be screened by genetic testing for the LMNA gene.

关 键 词：lamin A/C dilated cardiomyopathy limb-girdle muscular dystrophy MUTATION sudden death 

分 类 号：R686[医药卫生—骨科学]