Autosomal dominant Emery-Dreifuss dystrophy due to mutations in rod domain of the lamin A/C gene

• Published in: Neurology Vol. 55; no. 2; pp. 275 - 280
• Main Authors: FELICE, K. J, SCHWARTZ, R. C, BROWN, C. A, LEICHER, C. R, GRUNNET, M. L
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 25-07-2000
• Subjects: Adolescent; Adult; Biological and medical sciences; Chromosome Aberrations - genetics; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 1; Diseases of striated muscles. Neuromuscular diseases; Exons; Female; Genes, Dominant - genetics; Humans; Laminin - genetics; Male; Medical sciences; Muscle, Skeletal - pathology; Muscular Dystrophy, Emery-Dreifuss - diagnosis; Muscular Dystrophy, Emery-Dreifuss - genetics; Muscular Dystrophy, Emery-Dreifuss - pathology; Mutation, Missense - genetics; Neurology; Pedigree; Human; Neuromuscular diseases; Nervous system diseases; Pathophysiology; Family study; Rod; Genetic disease; Case study; Polymerase chain reaction; Emery Dreifuss muscular dystrophy; Gene; Mutation; Molecular biology
• ISSN: 0028-3878; 1526-632X
• DOI: 10.1212/WNL.55.2.275

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.
Clinical, pathologic, and genetic data are provided on two families with EDMD-AD.
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.
Mutations in the rod domain of the lamin A/C gene may cause the full clinical spectrum of EDMD-AD.