RESUMEN
BACKGROUND: Classic aniridia is a highly penetrant autosomal dominant disorder characterised by congenital absence of the iris, foveal hypoplasia, optic disc anomalies and progressive opacification of the cornea. >90% of cases of classic aniridia are caused by heterozygous, loss-of-function variants affecting the PAX6 locus. METHODS: Short-read whole genome sequencing was performed on 51 (39 affected) individuals from 37 different families who had screened negative for mutations in the PAX6 coding region. RESULTS: Likely causative mutations were identified in 22 out of 37 (59%) families. In 19 out of 22 families, the causative genomic changes have an interpretable deleterious impact on the PAX6 locus. Of these 19 families, 1 has a novel heterozygous PAX6 frameshift variant missed on previous screens, 4 have single nucleotide variants (SNVs) (one novel) affecting essential splice sites of PAX6 5' non-coding exons and 2 have deep intronic SNV (one novel) resulting in gain of a donor splice site. In 12 out of 19, the causative variants are large-scale structural variants; 5 have partial or whole gene deletions of PAX6, 3 have deletions encompassing critical PAX6 cis-regulatory elements, 2 have balanced inversions with disruptive breakpoints within the PAX6 locus and 2 have complex rearrangements disrupting PAX6. The remaining 3 of 22 families have deletions encompassing FOXC1 (a known cause of atypical aniridia). Seven of the causative variants occurred de novo and one cosegregated with familial aniridia. We were unable to establish inheritance status in the remaining probands. No plausibly causative SNVs were identified in PAX6 cis-regulatory elements. CONCLUSION: Whole genome sequencing proves to be an effective diagnostic test in most individuals with previously unexplained aniridia.
Asunto(s)
Aniridia , Anomalías del Ojo , Humanos , Factor de Transcripción PAX6/genética , Aniridia/genética , Mutación/genética , Anomalías del Ojo/genética , Exones , Proteínas de Homeodominio/genética , Proteínas del Ojo/genética , LinajeRESUMEN
We are facing a pandemic that is going to affect a significant part of the population. At the end of April in the world there are about 3,000,000 cases, with 205,000 deaths and 860,000 patients recovered. The response to this pandemic has in many cases led to a significant change in the daily work of caring for cancer patients, the good results of which depend largely on time-adjusted protocols and multidisciplinary treatments. We present a review of local, surgical and radiotherapy treatment together with authors' recommendations made from personal experience on ways to act in the diagnosis and surgical treatment of breast cancer during the COVID-19 pandemic. The multidisciplinary Breast Committees must continue to meet weekly in videoconference format. All surgical actions and irradiations must be carried out with maximum safety for both the patients and the participating teams. Hypofractionation in radiation therapy should be the standard treatment. Sometimes it is recommended to apply a primary systemic treatment or even a primary irradiation. Great coordination between the surgical and oncology teams, both medical and radiotherapeutic, is essential
Nos enfrentamos a una pandemia que afecta a una parte importante de la población. A finales de abril de 2020, en el mundo hay cerca de 3.000.000 de casos, con 205.000 muertes y 860.000 pacientes recuperados. La respuesta a esta pandemia en muchos casos ha supuesto modificaciones importantes en el cuidado diario de las pacientes con cáncer, dependiendo el buen resultado en buena parte del ajuste de los protocolos a las circunstancias especiales y a los tratamientos multidisciplinarios. Presentamos una revisión del tratamiento quirúrgico y radioterapia junto con las recomendaciones de los autores basadas en su experiencia personal a la hora del diagnóstico y tratamiento locorregional del cáncer de mama durante la pandemia del COVID-19. Los comités multidisciplinarios deben seguir reuniéndose semanalmente en formato de videoconferencia. Todos las intervenciones quirúrgicas e irradiaciones deben ser llevadas a cabo con la máxima seguridad tanto para las pacientes como para el personal sanitario que participa. El hipofraccionamiento debe ser el tratamiento radioterápico estándar. En algunos casos se utilizará tratamiento sistémico primario o incluso radioterapa preoperatoria. Es esencial una coordinación importante entre los equipos quirúrgicos y los oncológicos, tanto radioterápicos como médicos
