PMC6054619_01
A novel missense mutation in LMNA causes LMNA-associated congenital muscular dystrophy. a Muscle biopsy tissue sections from patients showing the histological features of muscular dystrophy. Bar: 50 microm. b Immunostaining for MHC class I in patient muscle sections. The sarcolemma and cytoplasm of non-necrotic muscle fibers are shown stained. Bar: 50 microm. c Sanger sequencing analysis of the patient. A novel missense heterozygous mutation was identified: c.115A>C (p.Asn39His) in exon 1 of LMNA. d Schematic of LMNA exons and corresponding protein domains. The location of the mutation identified in this study is indicated by a black arrow. e Alignment of the lamin A amino acid sequence in different species. The open red box indicates identical amino acids among all species. The blue box indicates acidic patches. The arrowhead indicates the position of the p.Asn39His mutation
41439_2018_18_Fig1_HTML.jpg
PMC6054619_01_41439_2018_18_Fig1_HTML.jpg
Fig1
Hematoxylin eosin staining of muscle biopsy specimens obtained from the biceps brachii showed scattered necrotic and regenerating fibers as well as marked variations in fiber size and marked endomysial fibrosis, suggesting chronic necrotic and regenerating processes compatible with muscular dystrophy (Fig. 1a). Immunohistochemical staining showed that muscle fibers were positive for MHC class I (Fig. 1b). A novel heterozygous missense mutation, c.115A>C (p.Asn39His), was detected in LMNA (Fig. 1c). The mutation was located within the 1A domain of the central rod domain, which has been implicated in dimerization in lamins (Fig. 1d). The asparagine caused by the mutation is highly conserved among species (Fig. 1e). Asn at 39, which is located at the 8th residue from the N-terminus in the coil 1A domain, is highly conserved during evolution (Fig. 1e).