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.
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.
Authors: Jop H van Berlo; Willem G de Voogt; Anneke J van der Kooi; J Peter van Tintelen; Gisèle Bonne; Rabah Ben Yaou; Denis Duboc; Tom Rossenbacker; Hein Heidbüchel; Marianne de Visser; Harry J G M Crijns; Yigal M Pinto Journal: J Mol Med (Berl) Date: 2004-11-13 Impact factor: 4.599
Authors: Benjamin E Hinz; Sydney G Walker; Austin Xiong; Rose A Gogal; Michael J Schnieders; Lori L Wallrath Journal: Int J Mol Sci Date: 2021-10-18 Impact factor: 5.923