RESUMEN
Trichothiodystrophy (TTD) is a rare hereditary disease whose prominent feature is brittle hair. Additional clinical signs are physical and neurodevelopmental abnormalities and in about half of the cases hypersensitivity to UV radiation. The photosensitive form of TTD (PS-TTD) is most commonly caused by mutations in the ERCC2/XPD gene encoding a subunit of the transcription/DNA repair complex TFIIH. Here we report novel ERCC2/XPD mutations affecting proper protein folding, which generate thermo-labile forms of XPD associated with thermo-sensitive phenotypes characterized by reversible aggravation of TTD clinical signs during episodes of fever. In patient cells, the newly identified XPD variants result in thermo-instability of the whole TFIIH complex and consequent temperature-dependent defects in DNA repair and transcription. Improving the protein folding process by exposing patient cells to low temperature or to the chemical chaperone glycerol allowed rescue of TFIIH thermo-instability and a concomitant recovery of the complex activities. Besides providing a rationale for the peculiar thermo-sensitive clinical features of these new cases, the present findings demonstrate how variations in the cellular concentration of mutated TFIIH impact the cellular functions of the complex and underlie how both quantitative and qualitative TFIIH alterations contribute to TTD clinical features.
Asunto(s)
Enfermedades del Cabello , Enfermedades de la Piel , Síndromes de Tricotiodistrofia , Xerodermia Pigmentosa , Humanos , Factor de Transcripción TFIIH/genética , Factor de Transcripción TFIIH/metabolismo , Síndromes de Tricotiodistrofia/genética , Síndromes de Tricotiodistrofia/complicaciones , Reparación del ADN , Enfermedades del Cabello/genética , Transcripción Genética , Xerodermia Pigmentosa/genética , Proteína de la Xerodermia Pigmentosa del Grupo D/genética , Proteína de la Xerodermia Pigmentosa del Grupo D/metabolismoRESUMEN
Amateur foraging, which can be described as the gathering of uncultivated plants for sustenance or recreation, supports many benefits for the forager and the environment; however, it can also present the hazard of unintentional poisoning. Asclepias syriaca, or common milkweed, is a potentially edible plant that also contains cardioactive steroids akin to digoxin. A 38-year-old female amateur forager boiled and sautéed 8-10 milkweed pods before ingesting them. She developed vomiting and heart palpitations within 1 hour and presented to an emergency department 3 hours after ingestion. Her exam was within normal limits with exception of heart rate in the 40-50s without hypotension. ECG was notable for sinus bradycardia. Laboratory analysis was notable for a detectable serum digoxin concentration. Life-threatening toxicity did not occur. Recently, some military services have advocated for foraging as a means to sustain far-forward troops. However, misidentification of plants by inexperienced foragers can result in severe toxicity or death. If mass foraging becomes part of expeditionary operations, military clinicians must be trained and prepared for the potentially severe plant-related poisonings.
RESUMEN
Bacterial endocarditis following atrial septal defect closure using Amplatzer device in a child is extremely rare. We report a 10-year-old girl who developed late bacterial endocarditis, 6 years after placement of an Amplatzer atrial septal occluder device. Successful explantation of the device and repair of the resultant septal defect was carried out using a homograft patch. The rare occurrence of this entity prompted us to highlight the importance of long-term follow up, review the management and explore preventive strategies for similar patients who have multiple co-morbidities and a cardiac device. A high index of suspicion is warranted particularly in pediatric patients.
