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Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene
Author(s) -
Mercuri E.,
Brown S. C.,
Nihoyannopoulos P.,
Poulton J.,
Kinali M.,
Richard P.,
Piercy R. J.,
Messina S.,
Sewry C.,
Burke M. M.,
McKenna W.,
Bonne G.,
Muntoni F.
Publication year - 2005
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20293
Subject(s) - lmna , lamin , exon , muscular dystrophy , genetics , weakness , muscle weakness , mutation , biology , skeletal muscle , gene mutation , emerin , gene , medicine , anatomy , nuclear protein , transcription factor
Abstract Mutations of the LMNA gene, encoding the nuclear envelope proteins lamins A and C, give rise to Emery–Dreifuss muscular dystrophy and to limb‐girdle muscular dystrophy 1B (EDMD and LGMD1B). With one exception, all the reported EDMD and LGMD1B mutations are confined to the first 10 exons of the gene. We report four separate cases, with mutations in the same codon of LMNA exon 11, characterized by remarkable variability of clinical findings, in addition to features not previously reported. One patient had congenital weakness and died in early childhood. In two other patients, severe cardiac problems arose early and, in one of these, cardiac signs preceded by many years the onset of skeletal muscle weakness. The fourth case had a mild and late‐onset LGMD1B phenotype. Our cases further expand the clinical spectrum associated with mutations in the LMNA gene and provide new evidence of the role played by the C‐terminal domain of lamin A. Muscle Nerve, 2005