Identification of a new lamin A/C mutation in a Chinese family affected with atrioventricular block as the prominent phenotype.
Even though mutations in LMNA have been reported in patients with typical dilated cardiomyopathy (DCM) and atrioventricular block (AVB) previously, the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval. Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2, where the LMNA gene was located. Direct DNA sequence analysis revealed a heterozygous G to A transition at nucleotide 244 in exon 1 of LMNA, which resulted in an E82K mutation. The E82K mutation co-segregated with all affected individuals in the family, and was not present in 200 normal controls. Further clinical evaluation of mutation carriers showed that 5 of 6 AVB patients exhibited mild DCM with a late onset of age in the fourth and fifth decades. Ejection fractions were documented in 5 patients with DCM, but 4 showed a normal value of > or = 50%. Echocardiography showed that atrial dilatation occurred earlier than ventricular dilatation in the patients. This study suggests that progressive AVB with normal QRS interval and accompanying DCM at later stages may represent a distinct type of DCM. The molecular mechanism by which the E82K mutation causes AVB as the prominent phenotype in DCM may be a focus of future studies.
Department of Pediatrics, Huazhong University of Science and Technology, Wuhan, 430022, China. xiaoyan8016@gmail.com
Xiaoyan
X
Wu
Qing K
QK
Wang
Le
L
Gui
Mugen
M
Liu
Xianqin
X
Zhang
Runming
R
Jin
Wei
W
Li
Lu
L
Yan
Rong
R
Du
Qiufen
Q
Wang
Jianfang
J
Zhu
Junguo
J
Yang
D000328:Adult; D044466:Asian People / Q000235:genetics; D054537:Atrioventricular Block / Q000150:complications / Q000235:genetics*; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
C494847:LMNA protein, human; D034904:Lamin Type A