RESUMEN
Described as the commonest single gene cause of learning disability internationally, the incidence of Fragile X syndrome (FXS) has never previously been determined in Ireland. The aim of this work was to determine the observed incidence of FXS in the island of Ireland; the Republic of Ireland (ROI) and Northern Ireland (NI) separately and combined. Ascertainment was achieved for a cross-sectional study by a retrospective, clinical and laboratory database review of positive FXS cases, born in either ROI or NI, between years 2000-2009 inclusive. The observed incidence of FXS per 10,000 live births in the island of Ireland in males was 0.94 (95%CI: 0.75-1.13) or â¼1:10,600 and in females was 0.23 (95%CI: 0.14-0.32) or â¼1:43,000. Comparable testing rates for FXS are present in ROI and NI, with on average 1.48% (1.30% in ROI, 1.96% in NI) of live male births and 0.4% (0.35% in ROI, 0.55% in NI) of live female births undergoing analysis which is comparable to other centres internationally. This study demonstrates the observed incidence of FXS in the island of Ireland is (i) approximately half the estimated worldwide incidence in males and is not explained by low levels of testing, and (ii) approximately one quarter the estimated worldwide incidence in females which may be explained by low levels of testing. © 2017 Wiley Periodicals, Inc.
Asunto(s)
Síndrome del Cromosoma X Frágil/epidemiología , Niño , Preescolar , Estudios Transversales , Femenino , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Pruebas Genéticas , Humanos , Incidencia , Lactante , Irlanda/epidemiología , Masculino , Mutación , Irlanda del Norte/epidemiología , Fenotipo , Vigilancia de la Población , Estudios RetrospectivosRESUMEN
The tumor suppressor protein p53 plays a critical role in the orchestration of the cellular responses to a variety of genotoxic and cytotoxic stresses. Mutations or functional inactivation of p53 seriously compromise these cellular processes and foster tumor development. p53 is the most frequently mutated gene in human cancers and over 90% of human non-melanoma skin cancers (NMSC) harbour p53 mutation. It plays a vital role in the control of the immediate and adaptive responses to ultraviolet radiation (UV) and the onset of NMSC. During the process of photocarcinogenesis, UV-specific p53 mutations occur early in the keratinocytes resulting in the loss of the wild type p53 function and continued UV exposure leads to clonal expansion of p53-mutated keratinocytes and promotion of skin tumors. Precisely how clones of keratinocytes containing such mutations, in an apparently normal epidermis, progress to a malignant carcinoma is unknown. Further examination of the functional significance of these UV-p53 mutations in affecting the immediate and adaptive responses of the skin to UV is critical to the development of effective prevention and therapeutic strategies for human skin cancer. The purpose of this article is to provide an overview of accumulating evidence pointing towards a critical role for p53 mutation in photocarcinogenesis.