STUDIO DELLE BASI GENETICHE NELLA SINDROME DELLA MORTE IMPROVVISA DEL LATTANTE (SIDS) E NELLA MORTE INASPETTATA DEL FETO (SIUD)

This study comes under the indications provided by the Law n.31 of February 2nd 2006 “Regulation for Diagnostic Post Mortem Investigation in Victims of Sudden Infant Death Syndrome (SIDS) and unexpected fetal death” that states the development of research programmes aimed to the reduction of the unexpected fetal death and the sudden infant death syndrome, that represent a major socio-medical problem. Currently, the literature doesn’t present in-depth investigations regarding the genetic bases of these pathologies, their incidence and the damaging effect of risk factors. Recent knowledge in the field of molecular genetics suggest a possible involvement of specific genes in the pathogenesis of these syndromes, particularly of SIDS, and the importance of interactions between genetic constitution and environmental factors in the fatal reflects unleashing. The major obstacle in the genetic research is represented by the complex characteristics of the human anatomic samples available. In fact, the autoptic biopsies are performed 24 h post-mortem and usually formalin-fixed. This common fixation procedure, even if is a traditional method of tissue preservation for the histopathological examination, compromises the quality and integrity of nucleic acids (DNA and in particular RNA). To solve this problem, in this Institute, a novel and innovative buffer, called RNAlater, has been introduced to preserve nucleic acids: samples treated with this buffer are comparable in quality with those obtained from fresh frozen tissues. In this way it is possible to store the samples at –20°C indefinitely, without significantly affecting the amount or the integrity of the recoverable nucleic acids. The main purpose of this thesis is to expand on the molecular genetic research, to identify the involvement of the serotonin transporter gene (5-HTT). In 2003 (Weese-Mayer DE et al.) the role of this gene has been confirmed in American and Japanese SIDS cases. This gene encodes for a membrane protein that regulates the uptake of the serotonin, a neurotransmitter with important roles during embryogenesis and autonomic nervous system differentiation. A new screening on Italian SIDS cases regarding the 5-HTT gene has been undertaken in our laboratory. The analysis has been extend to SIUD cases and to relating controls.