No abstract

Copy number variants and indels in 251 families with evidence of X-linked intellectual disability (XLID) were investigated by array comparative genomic hybridization on a high-density oligonucleotide X chromosome array platform. We identified pathogenic copy number variants in 10% of families, with mutations ranging from 2 kb to 11 Mb in size. The challenge of assessing causality was facilitated by prior knowledge of XLID-associated genes and the ability to test for cosegregation of variants with disease through extended pedigrees. Fine-scale analysis of rare variants in XLID families leads us to propose four additional genes, PTCHD1, WDR13, FAAH2, and GSPT2, as candidates for XLID causation and the identification of further deletions and duplications affecting X chromosome genes but without apparent disease consequences. Breakpoints of pathogenic variants were characterized to provide insight into the underlying mutational mechanisms and indicated a predominance of mitotic rather than meiotic events. By effectively bridging the gap between karyotype-level investigations and X chromosome exon resequencing, this study informs discussion of alternative mutational mechanisms, such as noncoding variants and non-X-linked disease, which might explain the shortfall of mutation yield in the well-characterized International Genetics of Learning Disability (IGOLD) cohort, where currently disease remains unexplained in two-thirds of families.

No abstract

Low back pain is one of the most common and important clinical, social, economic, and public health problems affecting the human population worldwide. The mechanism of radicular pain in the lumbar region is multifactorial but is likely due to mechanical and/or inflammatory factors. The natural history of disc herniation tends to be favourable. The Italian Society for Oxygen-Ozone Therapy (SIOOT) and the Italian Society for Spinal Surgery (SICV) guidelines recommend a conservative therapeutic approach. The biological action of medical ozone is still under investigation but some mechanisms of action have been proposed to explain its efficacy in disc herniation treatment: i) reduction of the inflammatory components; ii) hyper-oxygenation of the area of interest; iii) diminishing the size of the herniation; iv) stimulation of the repair process. The primary objective of this pilot study was to compare pain and function scores from patients before and after the treatment with Regenerative Selective Disc. The metrics that were established to define significant improvement were: i) improvement >1.8 on the Visual Analogue Scale (VAS) score; ii) improvement of 1 level or more on the modified Macnab criteria; iii) improvement >15% on the Oswestry Disability Index (ODI). Primary endpoints of this study were changes in the pretreatment and 1 month post treatment VAS, ODI and Macnab scores of the patients. After treatment results show that the patient population’s mean VAS, ODI and modified Macnab scores improved beyond the significant improvement scores. In fact, results showed that the mean patient’s population improvement scores were 2.9 for VAS, 22 for ODI and 1.4 for modified Macnab. Additionally, significant improvements were shown for 87% of the patients for VAS scale (>2.0), 80% of the patients for the ODI scale (>15 points) and 80% patients for the modified Macnab criteria (>1 point).