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Dominant lamin A/C gene mutations can be associated with muscular dystrophy and peripheral neuropathy
Author(s) -
Benedetti S,
Previtali S,
Toniolo D,
Iannaccone S,
Sferrazza B,
Comi G,
Carrera P,
Ferrari M,
Quattrini A,
Bertini E
Publication year - 2004
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1085-9489.2004.009209ad.x
Subject(s) - lmna , muscle biopsy , muscular dystrophy , myopathy , medicine , lamin , pathology , compound heterozygosity , peripheral neuropathy , cardiomyopathy , genetics , biology , mutation , endocrinology , biopsy , gene , heart failure , diabetes mellitus
The coexistence of neurogenic and myogenic etiology in scapuloperoneal syndrome was not previously ascribed to a single gene. Defects in the lamin A/C gene (LMNA) have been associated with a variety of pathologies, affecting mainly muscular and adipose tissues, although recently reported also in autosomal recessive CMT2. We describe here two patients associating features of myopathy and neuropathy linked to dominant LMNA mutations. Patient 1 presented with distal weakness at lower limbs and elevated serum CK. Neurophysiological studies revealed a sensorimotor axonal neuropathy, whereas muscle biopsy showed signs of both neurogenic and myogenic features. Molecular analysis of LMNA gene revealed a heterozygous R571C substitution. Patient 2 presented with mild proximal weakness and fatigability. She was carrying a pacemaker for cardiac arrhythmia and had a family history of sudden death. Electronmyography showed mild myopathic changes. A muscle biopsy revealed chronic myogenic and neurogenic features including atrophic angular fibers and type grouping. Analysis of the LMNA gene showed a heterozygous four nucleotides deletion in exon 5 (864del4), leading to premature protein truncation. The same mutation was found in the asymptomatic younger brother. This report describes for the first time dominantly‐inherited alterations of the nuclear lamins affecting both muscle and peripheral nerve, and the clinical heterogeneity of LMNA mutations.