Laser Therapy After Repair of the Distal Half of the Median Nerve; a Comparative Study

Background: Nerve injuries resulting from major or minor trauma often cause some disabilities for patients. Neurotmesis, characterized by complete anatomical rupture of the nerve, is the most severe form of the injury which will not recover without reconstructive surgery and nowadays such neural damages are improved by microsurgical procedures. Some studies have used low power laser for nerve cell growth in order to improve the rehabilitation results of peripheral nerves. Low power laser can complement the reformation of postsurgical nerve injuries. Objectives: The current study aimed to assess the effects of laser therapy after repair of median nerve rupture in the distal third of the forearm and to compare the results with that of the standard method. Patients and Methods: The current study was a case-control clinical trial of 36 patients with volar surface rupture of the distal third of forearm admitted to the emergency ward of Hazrat-e-Fatemeh Hospital within 72 hours of injury, they had anesthesia in the first, second, and third fingers as a result of Median Nerve Injury. Patients were divided into two groups. The first group included subjects treated with standard methods and the second group included those treated with low power laser therapy (LT) along with the standard method. The same surgeon operated the subjects in the two groups. The second group underwent 10 sessions of LT every other day. Clinical Examination, Electromyography and Nerve Conduction Velocity (NCV) were done after six months and the results were compared. Results: In the two -point discrimination- test, there was no significant difference between the two groups in the thumbs but a significant improvement was observed in the index finger of the LT group. Improvement of muscular examinations such as opposition and thumb abduction supported the usage of laser in the second group. Regarding electromyography and NCV, significant statistical difference was observed in the motor part of the laser group and, to a great extent, was compatible with the physical examinations. Conclusions: Accordingly, laser therapy in our protocol seemed to affect some of the nerve growth parameters, mostly on motor rather than sensory fibers. Copyright © 2015, Trauma Monthly

Analysis of KRT5 and KRT14 gene mutations and mode of inheritance in Iranian patients with clinical suspicion of Epidermolysis bullosa simplex

Background: Epidermolysis bullosa simplex is a hereditary skin disorder caused by mutations in several genes such as KRT5 and KRT14. Skin fragility in basal keratinocytes presence regions led to the cytolysis of epidermis and blistering. Aim of this study was to detect the molecular defects in KRT5 and KRT14 genes hot spots in patients with clinical suspicion of EBS and investigation of their probable genotype-phenotype correlations. Methods: Exons 1 and 6-7 of KRT5 and exons 1 and 4-7 of KRT14 amplification and mutation detection were performed by polymerase chain reaction and Sanger sequencing, respectively. Novel variants pathogenicity evaluated by bioinformatics tools. Results: Nine important variants detected in seven different patients within 6 Iranian families affected by Epidermolysis bullosa simplex, of which four variants were novel. Three patients had a mottled pigmentation phenotype G96D (p. Gly96Asp) and F97I (p. Phe97Ile) in KRT5. One of them showed a Dowling-Meara phenotype A417P (p. Ala417Pro) and E477D (p. Glu477Asp) in KRT5 and another had a Koebner type phenotype R397I (p. Arg397Ile) and Q444* (p. Gln444Ter) in KRT5. A novel variant G92E (p. Gly92Glu) in KRT5 in a double heterozygous state with a challenging variant A413T (p. Ala413Thr) in KRT14 identified in one patient with Koebner type phenotype. Also, a previously reported mutation I377T (p. Ile377Thr) in KRT14 gene identified in this study. Conclusion: The results of molecular data analysis showed that the most severe phenotypes were associated with mutations in highly conserved regions. In some cases, different inheritance modes were observed. © Iran University of Medical Sciences

Partial Loss of USP9X Function Leads to a Male Neurodevelopmental and Behavioral Disorder Converging on Transforming Growth Factor beta Signaling

BACKGROUND: The X-chromosome gene USP9X encodes a deubiquitylating enzyme that has been associated with neurodevelopmental disorders primarily in female subjects. USP9X escapes X inactivation, and in female subjects de novo heterozygous copy number loss or truncating mutations cause haploinsufficiency culminating in a recognizable syndrome with intellectual disability and signature brain and congenital abnormalities. In contrast, the involvement of USP9X in male neurodevelopmental disorders remains tentative.METHODS: We used clinically recommended guidelines to collect and interrogate the pathogenicity of 44 USP9X variants associated with neurodevelopmental disorders in males. Functional studies in patient-derived cell lines and mice were used to determine mechanisms of pathology.RESULTS: Twelve missense variants showed strong evidence of pathogenicity. We define a characteristic phenotype of the central nervous system (white matter disturbances, thin corpus callosum, and widened ventricles); global delay with significant alteration of speech, language, and behavior; hypotonia; joint hypermobility; visual system defects; and other common congenital and dysmorphic features. Comparison of in silico and phenotypical features align additional variants of unknown significance with likely pathogenicity. In support of partial loss-of-function mechanisms, using patient-derived cell lines, we show loss of only specific USP9X substrates that regulate neurodevelopmental signaling pathways and a united defect in transforming growth factor signaling. In addition, we find correlates of the male phenotype in Usp9x brain-specific knockout mice, and further resolve loss of hippocannpal-dependent learning and memory.CONCLUSIONS: Our data demonstrate the involvement of USP9X variants in a distinctive neurodevelopmental and behavioral syndrome in male subjects and identify plausible mechanisms of pathogenesis centered on disrupted transforming growth factor beta signaling and hippocampal function.Genetics of disease, diagnosis and treatmen

HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder

Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an essential, ubiquitously abundant protein involved in mRNA processing. Genetic variants in other members of the HNRNP family have been associated with neurodevelopmental disorders. Here, we describe 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five of them bear an identical in-frame deletion of nine amino acids in the extreme C terminus. To study the effect of this recurrent variant as well as HNRNPC haploinsufficiency, we used induced pluripotent stem cells (iPSCs) and fibroblasts obtained from affected individuals. While protein localization and oligomerization were unaffected by the recurrent C-terminal deletion variant, total HNRNPC levels were decreased. Previously, reduced HNRNPC levels have been associated with changes in alternative splicing. Therefore, we performed a meta-analysis on published RNA-seq datasets of three different cell lines to identify a ubiquitous HNRNPC-dependent signature of alternative spliced exons. The identified signature was not only confirmed in fibroblasts obtained from an affected individual but also showed a significant enrichment for genes associated with intellectual disability. Hence, we assessed the effect of decreased and increased levels of HNRNPC on neuronal arborization and neuronal migration and found that either condition affects neuronal function. Taken together, our data indicate that HNRNPC haploinsufficiency affects alternative splicing of multiple intellectual disability-associated genes and that the developing brain is sensitive to aberrant levels of HNRNPC. Hence, our data strongly support the inclusion of HNRNPC to the family of HNRNP-related neurodevelopmental disorders