Background Inherited mutations cause approximately 35 percent of cases of dilated cardiomyopathy; however, few genes associated with this disease have been identified. Previously, we located a gene defect that was responsible for autosomal dominant dilated cardiomyopathy and conduction-system disease on chromosome 1p1–q21, where nuclear-envelope proteins lamin A and lamin C are encoded by the LMNA (lamin A/C) gene. Mutations in the head or tail domain of this gene cause Emery–Dreifuss muscular dystrophy, a childhood-onset disease characterized by joint contractures and in some cases by abnormalities of cardiac conduction during adulthood. Methods We evaluated 11 families with autosomal dominant dilated cardiomyopathy and conduction-system disease. Sequences of the lamin A/C exons were determined in probands from each family, and variants were confirmed by restriction-enzyme digestion. The genotypes of the family members were ascertained. Results Five novel missense mutations were identified: four in the α...

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Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.

https://www.cell.com/cell/pdf/S0092-8674(01)00242-2.pdf

The Genetic Basis for Cardiomyopathy: from Mutation Identification to Mechanistic Paradigms

Organization of the higher-order chromatin loop: specific DNA attachment sites on nuclear scaffold

The A, B and C lamins are the major proteins of the nuclear envelope. The complete nucleotide sequence of the coding region of the A and C lamins shows that these proteins are identical except for their carboxy termini. The most prominent structural feature of both lamins is an alpha-helical region of repeating heptads of amino acids that shows striking homology with the entire family of cytoplasmic intermediate filament proteins. These features suggest that the nuclear envelope is made up of a network of coiled-coil polymers.

Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins.

The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis

https://www.cell.com/cell/pdf/0092-8674(80)90409-2.pdf

Larry Gerace

Papers

The nuclear envelope lamina is reversibly depolymerized during mitosis