Pathogenesis of congenital diaphragmatic hernia: additional clues regarding the involvement of the endothelin system.

Congenital diaphragmatic hernia (CDH) has an incidence of around 1/3,000 births. The pathogenesis of this developmental anomaly remains largely unknown and the description of small chromosomal imbalances in cases of CDH is of major interest for the identification of candidate genes. We report on a tandem 4q31.23 triplication encompassing the EDNRA gene identified by array-CGH in a male presenting an isolated left postero-lateral CDH. This copy number variation was inherited from the asymptomatic father, carrier of a size-identical duplication. We demonstrate that EDNRA mRNA is over-expressed in the proband in blood tissue. Consistent with the expression of EDNRA in the developing diaphragm and the observation that the endothelin system is up-regulated in human and animal models of CDH, we conclude that the EDNRA triplication may be the cause of CDH in our patient.

In vivo Real-Time Mass Spectrometry for Guided Surgery Application.

Here we describe a new instrument (SpiderMass) designed for in vivo and real-time analysis. In this instrument ion production is performed remotely from the MS instrument and the generated ions are transported in real-time to the MS analyzer. Ion production is promoted by Resonant Infrared Laser Ablation (RIR-LA) based on the highly effective excitation of O-H bonds in water molecules naturally present in most biological samples. The retrieved molecular patterns are specific to the cell phenotypes and benign versus cancer regions of patient biopsies can be easily differentiated. We also demonstrate by analysis of human skin that SpiderMass can be used under in vivo conditions with minimal damage and pain. Furthermore SpiderMass can also be used for real-time drug metabolism and pharmacokinetic (DMPK) analysis or food safety topics. SpiderMass is thus the first MS based system designed for in vivo real-time analysis under minimally invasive conditions.