ABSTRACT
POLA1 encodes the catalytic unit of DNA polymerase α, which together with the Primase complex launches the DNA replication process. While complete deficiency of this essential gene is presumed to be lethal, at least two conditions due to partial POLA1 deficiency have been described. The first genetic syndrome to be mapped to POLA1 was X-linked reticulate pigmentary disorder (XLPDR, MIM #301220), a rare syndrome characterized by skin hyperpigmentation, sterile multiorgan inflammation, recurrent infections, and distinct facial features. XLPDR has been shown to be accompanied by profound activation of type I interferon signaling, but unlike other interferonopathies, it is not associated with autoantibodies or classical autoimmunity. Rather, it is accompanied by marked Natural Killer (NK) cell dysfunction, which may explain the recurrent infections seen in this syndrome. To date, all XLPDR cases are caused by the same recurrent intronic mutation, which results in gene missplicing. Several hypomorphic mutations in POLA1, distinct from the XLPDR intronic mutation, have been recently reported and these mutations associate with a separate condition, van Esch-O'Driscoll syndrome (VEODS, MIM #301030). This condition results in growth retardation, microcephaly, hypogonadism, and in some cases, overlapping immunological features to those seen in XLPDR. This review summarizes our current understanding of the clinical manifestations of POLA1 gene mutations with an emphasis on its immunological consequences, as well as recent advances in understanding of its pathophysiologic basis and potential therapeutic options.
Subject(s)
DNA Polymerase I/deficiency , DNA Polymerase I/genetics , Immune System Diseases/genetics , Intellectual Disability/genetics , Nervous System Malformations/genetics , Animals , Genes, X-Linked/genetics , Humans , Mutation/geneticsABSTRACT
OBJECTIVE: This study seeks to identify, through a survey, how Peruvian gastroenterologists deal with Helicobacter pylori infection. MATERIAL AND METHODS: Gastroenterologists answered a survey concerning diagnosis and treatment of Helicobacter pylori infection. RESULTS: 177 valid answers were obtained (29.6% of the population). Within the main results, 77.4% use endoscopy + biopsy (histology) for diagnosis, 95.5% choose proton pump inhibitor + clarithromycin + amoxicillin as first line treatment and 50.0% check for eradication 4-6 weeks after treatment. CONCLUSIONS: Most gastroenterologists in Peru deal adequately with Helicobacter pylori infection, although follow-up aspects could be improved.
Subject(s)
Gastroenterologists , Helicobacter Infections , Practice Patterns, Physicians'/statistics & numerical data , Aftercare/methods , Aftercare/statistics & numerical data , Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Biopsy/statistics & numerical data , Clarithromycin/therapeutic use , Drug Therapy, Combination , Endoscopy, Gastrointestinal/statistics & numerical data , Female , Health Care Surveys , Helicobacter Infections/diagnostic imaging , Helicobacter Infections/drug therapy , Helicobacter Infections/pathology , Humans , Male , Peru , Proton Pump Inhibitors/therapeutic useABSTRACT
Identificar el manejo de la infección por Helicobacter pylori usado por los gastroenterólogos peruanos mediante una encuesta. Material y métodos: Se presentó una encuesta sobre el manejo de Helicobacter pylori a los gastroenterólogos. Resultados: Se obtuvo 177 encuestas válidas (29,6% de la población). Entre los resultados principales se observó que 77,4% usa la endoscopía digestiva alta + biopsia (histología) para el diagnóstico, 95,5% opta por un inhibidor de la bomba de protones + amoxicilina + claritromicina como tratamiento de primera línea y 50,0% revalúa a sus pacientes para determinar erradicación 4-6 semanas luego de culminarlo. Conclusiones: La mayoría de gastroenterólogos en el Perú maneja adecuadamente la infección por Helicobacter pylori, aunque lo referente a la revaluación podría mejorar...
This study seeks to identify, through a survey, how Peruvian gastroenterologists deal with Helicobacter pylori infection. Material and Methods: Gastroenterologists answered a survey concerning diagnosis and treatment of Helicobacter pylori infection. Results: 177 valid answers were obtained (29.6% of the population). Within the main results, 77.4% use endoscopy + biopsy (histology) for diagnosis, 95.5% choose proton pump inhibitor + clarithromycin + amoxicillin as first line treatment and 50.0% check for eradication 4-6 weeks after treatment. Conclusions: Most gastroenterologists in Peru deal adequately with Helicobacter pylori infection, although follow-up aspects could be improved...