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Mutations in Lamin A/C and their binding partners and nuclear envelope phenotype in cardiomyocytes from Dilated cardiomoyopathy patients
Author(s) -
Gupta Pallavi,
Bilinska Zofia,
Sylvius Nicolas,
Veinot John,
Bolongo Pierrette,
Boudreau Emilie,
Jackson Tracy,
Tesson Frederique
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a182-a
Subject(s) - lamin , mutation , nuclear lamina , gene , gene mutation , biology , genetics , somatic cell , lmna , phenotype , germline mutation , dilated cardiomyopathy , microbiology and biotechnology , nuclear protein , medicine , heart failure , transcription factor
Lamin A/C gene is one of most frequently reported mutated genes in dilated cardiomyopathy which is characterized by the dilatation of cardiac chambers and impaired contraction. Lamin A and C are major components of the nuclear lamina. From a cohort of DCM patients, we selected seven patients displaying major cardiomyocytes nucleus envelope abnormalities on electron microscopy images. In the DNA from these patients, we screened both Lamin A/C and thymopoietin genes for mutations by direct sequencing. Thymopoietin is the only lamin A/C binding partner previously shown to harbor a mutation in a DCM patient. Only one of these seven patients carried a mutation in the lamin A/C gene. No patient carried a mutation in the thymopoietin gene. In our control population of DCM patients with normal ultrastructural phenotype, two patients bore a lamin A/C gene mutation; none had a mutation in the thymopoietin gene. Taken together, our results suggest that patients with a clinical suspicion of lamin A/C mutation and with marked abnormality of cardiomyocytes nuclei might be free of both lamin A/C and thymopoietin germline mutation. These patients may therefore carry a mutation in another gene encoding a protein involved in the maintenance of the nuclear architecture or a somatic mutation. Furthermore, the occurrence of mutation in one of these genes does not necessary lead to cardiomyocyte nuclear envelope defects.