R25G mutation in exon 1 of LMNA gene is associated with dilated cardiomyopathy and limb-girdle muscular dystrophy 1B.
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.
Yuan
Wo-liang
WL
Department of Cardiovascular Medicine, Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Huang
Chun-yan
CY
Wang
Jing-feng
JF
Xie
Shuang-lun
SL
Nie
Ru-qiong
RQ
Liu
Ying-mei
YM
Liu
Pin-ming
PM
Zhou
Shu-xian
SX
Chen
Su-qin
SQ
Huang
Wei-jun
WJ
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D005091:Exons; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D009154:Mutation
D034904:Lamin Type A; C440308:lamin C