Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.

Purpose The treatment of symptomatic Schwannoma is surgical excision. However, in the case of major peripheral nerves with motor function, there are concerns including neurological complications following surgery. This study was designed to evaluate the surgical outcome of Schwannomas originating from major peripheral nerves of the lower limb. Additionally, we sought to find out the predictable factors for permanent neurological deficits. Methods Between 2004 and 2008, 30 consecutive Schwannomas underwent simple excision or enucleation. Surgical outcomes after excision were evaluated with an emphasis on neurological deficits and recurrence. Neurological complications were classified as major or minor neurological deficits and evaluated immediately after surgery and at final follow-up. Risk factors for development of neurological deficits were identified. Results Twenty-three patients (23/30, 76.7 %) developed neurological deficits immediately after surgery. After a mean of 58.8 months (32-79 months), 19 patients (19/30, 63.3 %) showed no residual neurological deficits. Among the remaining 11 (11/30, 36.7 %), nine patients had tolerable symptoms and two patients had major neurological deficits including significant motor weakness and sensory impairments. Larger tumours tended to be at greater risk of neurological deficit after surgery. One recurrence of the tumour was seen two years after surgery. There were no cases of reoperation or malignant transformation Conclusions In the majority of cases, Schwannomas in the lower limb can be excised with acceptable risk for neurological deficits. However, meticulous dissection is required in large-sized Schwannomas because these tumours seem to have a higher frequency of fascicular injury during dissection.

The purpose of this study was to assess the diagnostic value of imaging-guided core needle biopsy for the diagnosis of musculoskeletal lesions. Between 2004 and 2007, 309 biopsies (ultrasound 151, computed tomography 89, and fluoroscopy 69) were included. There were 142 soft tissue and 167 bony lesions. Diagnostic yields and accuracies were assessed using the chi-square test or Fisher's exact test with Bonferroni's correction when necessary. Overall diagnostic yield was 90.6% for all 309 lesions (bone 91.6% vs. soft tissue 89.3%, p = 0.5125). The diagnostic accuracy of the 185 core needle biopsies, which were confirmed by definitive surgical biopsies, was 84.3% (bone 88.9% vs. soft tissue 79.1%, p = 0.0669). The yields of homogenous bone tumours (96.8%) were not significantly higher than those of bone tumours with a heterogenic architecture (86.4%, p = 0.0794). The difference between accuracies for homogenous bone tumours (89.1%) and heterogenous bone tumours (85.0%) was not significant (p = 0.6930). However, for soft tissue tumours, homogenous tumours had a significantly higher diagnostic yield than heterogenous tumours (97.5% vs. 81.4%, p = 0.0036). Diagnostic accuracy for homogenous tumours was also significantly higher than that for heterogenous soft tissue tumours (94.4% vs. 60.6%, p < 0.0001). The image-guided percutaneous needle biopsy of musculoskeletal lesions is a safe and effective procedure if it is performed selectively in soft tissue tumours with homogenous architectures.