RESUMEN
Sudden infant death syndrome (SIDS) is currently the major cause of an unexpected and unexplained death of infants in the first year of lifetime in industrialized countries. Besides environmental factors also genetic factors have been identified as risk factors for SIDS. Notably, the mutation c.457dupG (p.Glu153Glyfs*17) in the TSPYL1 gene has been reported to cause autosomal recessive sudden infant death with dysgenesis of the testes syndrome (SIDDT) in an Old Order Amish community in Pennsylvania. The purpose of this study was to analyze whether variants of TSPYL1 are associated with the sudden infant death syndrome (SIDS) in the area of Europe from which the Amish descended. Mutation analysis of the entire TSPYL1 gene was performed in a cohort of 165 SIDS cases with mostly Swiss ethnic origin, in comparison to 163 German controls. Eight known polymorphisms were detected, none of which was significantly associated with SIDS. One deceased girl was heterozygous for the hitherto unreported TSPYL1 variant c.106C>G (p.Leu36Val), and two affected girls were heterozygous for the rare known TSPYL1 variant rs140756663 (c.1098C>A, p.Phe366Leu). In addition, one deceased boy was heterozygous for the rare common silent nucleotide substitution c.718C>T (p.Leu240Leu, rs150144081), while one control was heterozygous for the rare silent nucleotide substitution rs56190632 (c.760C>T; p.Leu254Leu). In silico analyses predicted a likely non-pathogenic effect for p.Leu36Val and p.Phe366Leu, respectively, although protein features might be affected. The Amish founder mutation was not detected in the analyzed SIDS cases and controls. Mutations and polymorphisms in the TSPYL1 gene were not associated with SIDS in a cohort of 165 deceased Swiss infants.
Asunto(s)
Proteínas Nucleares/genética , Muerte Súbita del Lactante/genética , Población Blanca/etnología , Población Blanca/genética , Estudios de Casos y Controles , Análisis Mutacional de ADN , Femenino , Estudios de Asociación Genética , Alemania , Humanos , Lactante , Recién Nacido , Masculino , Mutación , Polimorfismo de Nucleótido Simple , Muerte Súbita del Lactante/etnología , Muerte Súbita del Lactante/patología , SuizaRESUMEN
Peripheral nerve injuries are frequently seen in trauma patients and due to delayed nerve repair, lifelong disabilities often follow this type of injury. Innovative therapies are needed to facilitate and expedite peripheral nerve regeneration. The purpose of this study was to determine the effects of a 1-time topical application of a 26-amino-acid fragment (C3(156-181)), derived from the Clostridium botulinum C3-exoenzyme, on peripheral nerve regeneration in 2 models of nerve injury and repair in adult rats. After sciatic nerve crush, different dosages of C3(156-181) dissolved in buffer or reference solutions (nerve growth factor or C3(bot)-wild-type protein) or vehicle-only were injected through an epineurial opening into the lesion sites. After 10-mm nerve autotransplantation, either 8.0 nmol/kg C3(156-181) or vehicle were injected into the proximal and distal suture sites. For a period of 3 to 10 postoperative weeks, C3(156-181)-treated animals showed a faster motor recovery than control animals. After crush injury, axonal outgrowth and elongation were activated and consequently resulted in faster motor recovery. The nerve autotransplantation model further elucidated that C3(156-181) treatment accounts for better axonal elongation into motor targets and reduced axonal sprouting, which are followed by enhanced axonal maturation and better axonal functionality. The effects of C3(156-181) are likely caused by a nonenzymatic down-regulation of active RhoA. Our results indicate the potential of C3(156-181) as a therapeutic agent for the topical treatment of peripheral nerve repair sites.
