High incidence of sudden cardiac death with conduction disturbances and atrial cardiomyopathy caused by a nonsense mutation in the STA gene.
BACKGROUND
The STA gene encodes emerin and is one of the genes that is affected in Emery-Dreifuss muscular dystrophy (EDMD). Although it has been reported that EDMD caused by the STA gene mutation is associated with X-linked recessive inheritance, the genotype-phenotype correlations, with special reference to cardiac manifestations, are not well defined.


RESULTS
We identified 16 carriers (7 male and 9 female) with a nonsense mutation in exon 6 of the STA gene in 2 EDMD families. Pacemakers were required for treatment of bradyarrhythmias in all 7 male carriers and in 2 of the 9 female carriers. In addition, 2 of the 9 female carriers displayed atrial fibrillation. In these 2 families, 3 males without pacemaker implantation, who were not tested genetically, had died suddenly. In these family members, the majority of carriers with the mutation had not been clinically diagnosed as having EDMD before genetic testing because of extremely mild or nonexistent skeletal myopathy.


CONCLUSIONS
EDMD caused by this mutation is characterized by atypical clinical features and incomplete penetrance of the clinical phenotype and may result in serious cardiac complications, including sudden death. Approaches to preventing possible sudden death in carriers with the STA gene mutation require further study.
Sakata
Kenji
K
Department of Molecular Genetics of Cardiovascular Disorders, Division of Cardiovascular Medicine,Graduate School of Medical Science, Kanazawa University, Takara-machi, Ishikawa, Japan.
Shimizu
Masami
M
Ino
Hidekazu
H
Yamaguchi
Masato
M
Terai
Hidenobu
H
Fujino
Noboru
N
Hayashi
Kenshi
K
Kaneda
Tomoya
T
Inoue
Masaru
M
Oda
Yoshio
Y
Fujita
Takashi
T
Kaku
Bunji
B
Kanaya
Hounin
H
Mabuchi
Hiroshi
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000235:genetics; D009202:Cardiomyopathies / Q000235:genetics*; D002675:Child, Preschool; D018389:Codon, Nonsense; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005192:Family Health; D005260:Female; D006325:Heart Atria / Q000503:physiopathology; D006327:Heart Block / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics; D009687:Nuclear Proteins; D010138:Pacemaker, Artificial; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D013946:Thymopoietins / Q000235:genetics*
D018389:Codon, Nonsense; D008565:Membrane Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin