Deletion of the LMNA initiator codon leading to a neurogenic variant of autosomal dominant Emery–Dreifuss muscular dystrophy

Mutations in the LMNA gene encoding the nuclear envelope protein, lamins A and C, have been associated with at least nine distinct disorders now called laminopathies, including Emery–Dreifuss muscular dystrophy and Charcot–Marie–Tooth type 2 disease. We identified a novel mutation in the 5′ region of the LMNA gene −3del15, resulting in the loss of 15 nucleotides from −3 to +12, including the translation ATG initiator codon. The mutation segregates in a previously described family with a clinical phenotype that shared features of both Emery–Dreifuss muscular dystrophy and Charcot–Marie–Tooth type 2. Thus, the mutation with this unique phenotypical expression represents the first example for a link between the neurogenic and myogenic phenotypes and extends the clinical variability of laminopathies.