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.
Walter
Maggie C
MC
Friedrich-Baur-Institute, Gene Center and Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, Germany.
Witt
Thomas N
TN
Weigel
Beate Schlotter
BS
Reilich
Peter
P
Richard
Pascale
P
Pongratz
Dieter
D
Bonne
Gisèle
G
Wehnert
Manfred S
MS
Lochmüller
Hanns
H
D000328:Adult; D018387:Codon, Initiator / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics* / Q000473:pathology
D018387:Codon, Initiator; D034904:Lamin Type A