RESUMEN
Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing, and bone fragility. Whole-exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A) as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss-of-function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut development and function.
Asunto(s)
Huesos/patología , Colestasis/genética , Diarrea/genética , Pérdida Auditiva/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación con Pérdida de Función/genética , Adolescente , Animales , Preescolar , Diarrea/fisiopatología , Familia , Femenino , Fibroblastos/patología , Motilidad Gastrointestinal , Humanos , Recién Nacido , Linfocitos/patología , Masculino , Linaje , Fenotipo , Síndrome , Adulto Joven , Pez CebraRESUMEN
The death or near death of a presumably healthy newborn in the delivery room is uncommon. We report here 6 cases of apparent life-threatening events (ALTEs) in the delivery room during the first 2 hours of life. In each case, the incident occurred in a healthy infant who was in a prone position on his or her mother's abdomen during early skin-to-skin contact. In most cases, the mother was primiparous, and in all cases the mother and infant were not observed during the initiation of skin-to-skin contact and breastfeeding. There are many benefits of early skin-to-skin contact and breastfeeding in the delivery room. However, in view of the risk of a rare but significant ALTE, we suggest that surveillance of newborns is needed. Although many ALTEs are apparently caused by obstruction, we suggest that a standardized investigational workup be performed after an ALTE.
Asunto(s)
Asfixia Neonatal/etiología , Posición Prona , Muerte Súbita del Lactante/etiología , Asfixia Neonatal/mortalidad , Lactancia Materna , Causas de Muerte , Hemorragia Cerebral/etiología , Hemorragia Cerebral/mortalidad , Estudios Transversales , Salas de Parto , Enfermedades en Gemelos , Femenino , Francia , Paro Cardíaco/etiología , Paro Cardíaco/mortalidad , Humanos , Hipoxia-Isquemia Encefálica/etiología , Hipoxia-Isquemia Encefálica/mortalidad , Incidencia , Recién Nacido , Masculino , Periodo Posparto , Resucitación , Factores de RiesgoRESUMEN
We report on the results of clinical evaluation of a newly developed system for wireless monitoring of pulse oximetry (SpO2), actimetry and position in infants. The sensors, electronics and the power supply were integrated into a specially designed infant shoe named BBA bootee. The comparative data collected in 71 babies yielded a mean (bias +/- SD) value of (-1.2 +/- 1.9) % for SpO2 and (-2 +/- 8) beats per minute for heart rate with regard to reference monitors. A reliable detection of infant's movements and prone position by an integrated 3-axes accelerometer has been validated by video observations. Combining the pulse oximetry and actimetry data, an algorithm is proposed to reduce the oximetry motion artifact and related false alarms. Ergonomics of the sensor-supporting garment is addressed.