PMC4921644_01
Clinical and dermatopathological findings in a patient carrying a novel LEMD3/Man1 (Trp620X) mutation. (a-c) Morphea lesions. (a) Skin lesions involving abdomen. Note indurated periumbilical skin. (b) Close-up highlighting ruptured periumbilical bulla. (c) Indurated skin on chest. (d-g) Histopathology from lesional skin. (d, f) Abdominal skin, H&E, 20x (d) and 50x (f). (e, g) Chest skin, H&E stain 20x (e) and 50x (g).
CRIDM2016-2483041.001.jpg
PMC4921644_01_CRIDM2016-2483041.001.jpg
fig1
Physical examination demonstrated firmly indurated and hyperpigmented lesions on the arms, shoulders, chest, belt line, and lower legs and scaly erythematous and partially bullous patches over both breasts (Figures 1(a)-1(c)). A punch biopsy of lesional skin yielded square-shaped tissue with fibrosis and a cellular infiltrate (Figures 1(d)-1(g)).
Histochemistry of lesional skin from patient with LEMD3 Trp620X mutation. (a) H&E stain. (b) Masson's trichrome staining. (c) Elastin staining. (a1), (b1), and (c1) represent 100x magnification of the epidermis, (a2), (b2), and (c2) represent 100x magnification of the dermis, and (a3), (b3), and (c3) show 630x magnification of the dermis. Note increase in both collagen and elastin deposition and irregular collagen fibrils.
CRIDM2016-2483041.002.jpg
PMC4921644_01_CRIDM2016-2483041.002.jpg
fig2
Masson's trichrome and elastin stains revealed dense dermal collagen deposition and increased elastic fiber accumulation (Figure 2).
Osteopoikilosis. Plain radiographs. (a) Foot. (b) Hand. (c) Knee. Note multiple small (1-5 mm) sclerotic periarticular lesions consistent with bony islands of osteopoikolosis (marked by arrows).
CRIDM2016-2483041.003.jpg
PMC4921644_01_CRIDM2016-2483041.003.jpg
fig3
Radiographs of the hands, feet, and knees revealed numerous well-demarcated bone densities (osteopoikilosis) bilaterally (Figure 3).
Characterization of novel LEMD3 mutation. (a) 3D predicted conformation of native and mutated p.Trp620X Man1 protein (EsyPred3d modeling software). Note deletion of the DNA-binding and R-Smad recognition domains. (b) Amino acid sequence of Man1; letters represent amino acids as defined by IUPAC. The Trp620X codon is indicated. (c) List of functional domains and presence of domains in normal and mutated Man1 protein. (d) DNA sequence of LEMD3, highlighting the novel c.1863G > A mutation.
CRIDM2016-2483041.004.jpg
PMC4921644_01_CRIDM2016-2483041.004.jpg
fig4
This nucleotide change is predicted to truncate Man1 at amino acid 621, resulting in deletion of the second transmembrane helical domain and DNA-binding and Smad-interacting domains (Figure 4).