RESUMO
BRCA1 and BRCA2 are major breast cancer susceptibility genes whose pathogenic variants are associated with a significant increase in the risk of breast and ovarian cancers. Current genetic screening is generally limited to BRCA1/2 exons and intron/exon boundaries. Most identified pathogenic variants cause the partial or complete loss of function of the protein. However, it is becoming increasingly clear that variants in these regions only account for a small proportion of cancer risk. The role of variants in non-coding regions beyond splice donor and acceptor sites, including those that have no qualitative effect on the protein, has not been thoroughly investigated. The key transcriptional regulatory elements of BRCA1 and BRCA2 are housed in gene promoters, untranslated regions, introns, and long-range elements. Within these sequences, germline and somatic variants have been described, but the clinical significance of the majority is currently unknown and it remains a significant clinical challenge. This review summarizes the available data on the impact of variants on non-coding regions of BRCA1/2 genes and their role on breast and ovarian cancer predisposition.
RESUMO
OBJECTIVE: To determine whether monitoring cerebral oxygen tissue saturation (StO2) with near-infrared spectroscopy (NIRS) and brain activity with amplitude-integrated electroencephalography (aEEG) can predict infants at risk for intraventricular hemorrhage (IVH) and death in the first 72 hours of life. STUDY DESIGN: A NIRS sensor and electroencephalography leads were placed on 127 newborns <32 weeks of gestational age at birth. Ten minutes of continuous NIRS and aEEG along with heart rate, peripheral arterial oxygen saturation, fraction of inspired oxygen, and mean airway pressure measurements were obtained in the delivery room. Once the infant was transferred to the neonatal intensive care unit, NIRS, aEEG, and vital signs were recorded until 72 hours of life. An ultrasound scan of the head was performed within the first 12 hours of life and again at 72 hours of life. RESULTS: Thirteen of the infants developed any IVH or died; of these, 4 developed severe IVH (grade 3-4) within 72 hours. There were no differences in either cerebral StO2 or aEEG in the infants with low-grade IVH. Infants who developed severe IVH or death had significantly lower cerebral StO2 from 8 to 10 minutes of life. CONCLUSIONS: aEEG was not predictive of IVH or death in the delivery room or in the neonatal intensive care unit. It may be possible to use NIRS in the delivery room to predict severe IVH and early death. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02605733.
Assuntos
Encéfalo/fisiopatologia , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/mortalidade , Doenças do Prematuro/etiologia , Doenças do Prematuro/mortalidade , Espectroscopia de Luz Próxima ao Infravermelho , Eletroencefalografia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , RessuscitaçãoRESUMO
Infants may benefit if resuscitation could be provided with an intact umbilical cord. Infants identified at risk for resuscitation were randomized to 1- or 5-minute cord clamping. The 5-minute group had greater cerebral oxygenation and blood pressure. Studies are needed to determine whether this translates into improved outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02827409.