Autosomal dominant Emery-Dreifuss dystrophy due to mutations in rod domain of the lamin A/C gene.
BACKGROUND
Autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD-AD) is a disorder characterized clinically by humeropelvic weakness, contractures, and cardiomyopathy, and genetically by mutations in the lamin A/C gene on 1q21.2-q21.3. Of the 14 lamin A/C gene mutations reported thus far, the four involving the rod domain have been associated with isolated cardiomyopathy and conduction-system disease. This is the first report of rod domain mutations in patients with the full EDMD-AD phenotype.


METHODS
Clinical, pathologic, and genetic data are provided on two families with EDMD-AD.


RESULTS
In both families, the full clinical spectrum of EDMD-AD was demonstrated. For the proband in family 1, sequence analysis detected a mutation within exon 2 of the lamin A/C gene. The missense mutation was due to a A448C base substitution causing a Thr150Pro amino acid change. For the proband of family 2, sequence analysis detected an in-frame 3-bp deletion (AAG 778-780 or 781-783) removing one of two adjacent lysine residues (K 260 or 261) of exon 4. Both mutations were in the central rod domain of the lamin A/C gene.


CONCLUSIONS
Mutations in the rod domain of the lamin A/C gene may cause the full clinical spectrum of EDMD-AD.
Felice
K J
KJ
Department of Neurology, Division of Human Genetics, University of Connecticut School of Medicine, Farmington, USA. felice.nso.uchc.edu
Schwartz
R C
RC
Brown
C A
CA
Leicher
C R
CR
Grunnet
M L
ML
D000293:Adolescent; D000328:Adult; D002869:Chromosome Aberrations / Q000235:genetics*; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D002878:Chromosomes, Human, Pair 1; D005091:Exons; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D007797:Laminin / Q000235:genetics*; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree
D007797:Laminin; C084098:laminin A