Objective: In this study, we investigated the detailed clinical findings and underlying genetic defect in 3 presumably related Bulgarian families displaying dominantly transmitted adult onset distal myopathy with upper limb predominance. Methods: We performed neurologic, electrophysiologic, radiologic, and histopathologic analyses of 13 patients and 13 at-risk but asymptomatic individuals from 3 generations. Genome-wide parametric linkage analysis was followed by bidirectional sequencing of the filamin C (FLNC) gene. We characterized the identified nonsense mutation at cDNA and protein level. Results: Based on clinical findings, no known myopathy subtype was implicated in our distal myopathy patients. Light microscopic analysis of affected muscle tissue showed no specific hallmarks; however, the electron microscopy revealed changes compatible with myofibrillar myopathy. Linkage studies delineated a 9.76 Mb region on chromosome 7q22.1-q35 containing filamin C (FLNC), a gene previously associated with myofibrillar myopathy. Mutation analysis revealed a novel c.5160delC frameshift deletion in all patients of the 3 families. The mutation results in a premature stop codon (p.Phe1720LeufsX63) that triggers nonsense-mediated mRNA decay. FLNC transcript levels were reduced in muscle and lymphoblast cells from affected subjects and partial loss of FLNC in muscle tissue was confirmed by protein analysis. Conclusions: The FLNC mutation that we identified is distinct in terms of the associated phenotype, muscle morphology, and underlying molecular mechanism, thus extending the currently recognized clinical and genetic spectrum of filaminopathies. We conclude that filamin C is a dosage-sensitive gene and that FLNC haploinsufficiency can cause a specific type of myopathy in humans.

Magnetic resonance urography (MRU) is one of the most attractive imaging modalities in paediatric urology, providing largest diagnostic information in a single protocol. Therefore, the aim of our study was to assess the diagnostic value of MRU in children with urogenital anomalies (especially anomalies of the renal pelvis and ureter) and the renal function using different post-processing functional software. Ninety six children (7 days - 18 years old) were examined. In 54 patients of them, a static T(2) MRU was completed by excretory T(1) MRU after gadolinium administration and functional analysis has been performed using two functional analysis softwares "CHOP-fMRU" and "ImageJ" software. MRU showed suspicious renal and the whole urinary tract anomalies with excellent image quality in all children. In ureteropelvic obstruction, MRU was confirmatory to the other imaging techniques, but it was superior modality concerning the evaluation of end-ureteral anomalies. There was an excellent correlation between the MRU data and diagnosis, determined by surgery. The renal transit times, renal volumes and volumetric differential renal function were assessed separately by "CHOP-fMRU" and "ImageJ" with excellent agreement with 99(m)Tc-DTPA and among them. MRU overcomes a lot of limitations of conventional imaging modalities and has a potential to become a leading modality in paediatric uroradiology. Synthesis of both anatomical and functional criteria in MR urography enables to select the best candidates for surgical treatment. Even small kidney dysfunction can be detected by functional analysis software.

Future of prostate imaging: Artificial intelligence in assessing prostatic magnetic resonance imaging

Background and objectives: To assess the pain relief of bipolar RFA combined or not with vertebroplasty in patients with painful vertebral metastases and to evaluate the feasibility and tolerance of the RFA procedure performed under local anesthesia. Materials and Methods: 25 patients (18 men, 7 women, mean age: 60.X y.o) with refractory painful vertebral metastasis were consecutively included between 2012 and 2019. A total of 29 radiofrequency ablation (RFA) procedures were performed under CT guidance, local anesthesia and nitrous oxide inhalation, including 16 procedures combined with vertebroplasty for bone consolidation purposes. Pain efficacy was clinically evaluated using the visual analogue scale (VAS) at day 1, 1 month, 3 months, 6 months and 12 months, and the tolerance of the procedure was evaluated. Results: Procedure tolerance was graded as either not painful or tolerable in 97% of cases. Follow-up postprocedure mean VAS score decrease was 74% at day 1: 6.6 (p < 0.001), 79% at 1 month: 6.6 (p < 0.001), 79% at 3 months: 6.5 (p < 0.001), 77% at 6 months, and 79% at 12 months: 6.6 (p < 0.001). Conclusions: Bipolar RFA, with or without combined vertebroplasty, appears to be an effective and reliable technique for the treatment of refractory vertebral metastases in patients in the palliative care setting. It is a feasible procedure under local anesthesia which is well tolerated by patients therefore allowing to broaden the indications of such procedures. Field of study: interventional radiology.

Disorders/differences of sexual development (DSD) are a group of conditions, some of which can be clinically indistinguishable mainly due to their phenotypic variability. Defining the molecular basis of their wide spectrum is still in progress. The diagnosis of 5-alpha-reductase type 2 (5α-reductase-2) deficiency is difficult especially in newborns and pre-pubertal individuals, and as a result its frequency might be underestimated. In the present study, we describe the clinical characteristics and molecular defects in 3 nonrelated 5α-reductase-2 deficiency patients of Bulgarian descent. Sequencing analysis revealed the mutations p.Y188CfsX9 and p.G196S, and MLPA analysis showed a deletion of exon 1 in the SRD5A2 gene. The observed genetic substitutions were not detected in 76 additionally screened unrelated controls, but a heterozygous healthy carrier of the p.R171S mutation was found. This is the first study on the molecular basis of 5α-reductase-2 deficiency in Bulgaria. It suggests that the carrier frequency of mutations in the SRD5A2 gene might be noteworthy worldwide. There is no correlation between cultural aspects, location, and/or population size and the number of different mutations in SRD5A2 detected, and more efforts should be made to determine the prevalence of this condition in different geographic areas. Our study supports the importance of genetic testing in 46,XY DSD patients, especially in countries or regions where 5α-reductase-2 deficiency has not been reported so far.