Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We performed whole-genome sequencing (WGS) in 197 individuals with unexplained DEE and pharmaco-resistant seizures and in their unaffected parents. We focused our attention on de novo mutations (DNMs) and identified candidate genes containing such variants. We sought to identify additional subjects with DNMs in these genes by performing targeted sequencing in another series of individuals with DEE and by mining various sequencing datasets. We also performed meta-analyses to document enrichment of DNMs in candidate genes by leveraging our WGS dataset with those of several DEE and ID series. By combining these strategies, we were able to provide a causal link between DEE and the following genes: NTRK2, GABRB2, CLTC, DHDDS, NUS1, RAB11A, GABBR2, and SNAP25. Overall, we established a molecular diagnosis in 63/197 (32%) individuals in our WGS series. The main cause of DEE in these individuals was de novo point mutations (53/63 solved cases), followed by inherited mutations (6/63 solved cases) and de novo CNVs (4/63 solved cases). De novo missense variants explained a larger proportion of individuals in our series than in other series that were primarily ascertained because of ID. Moreover, these DNMs were more frequently recurrent than those identified in ID series. These observations indicate that the genetic landscape of DEE might be different from that of ID without epilepsy.

A renin-like enzyme is present in brain tissue and is independent of kidney and plasma renin. In the presence of homologous substrate it forms angiotensin. Administration of aldosterone significantly decreases this angiotensinforming enzyme activity, while administration of progesterone markedly enhances it.

The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.

Plasma arginine vasopressin (PAV) concentration was determined by radioimmunoassay during the diurnal cycle in 8 recombent healthy male subjects. Two subjects were studied again 3 weeks later while receiving 1 mycles. In 8 out of 10 cycles, a nocturnal increase in PAV was found; there was a progressive rise during the night in 5 subjects and a peak occurred at 2400 or 3400 h. In 1 subject no variation was detected and in another, the pattern was compleetly different. The mean PAV in the 10 cycles was significantly (P less than 0.001) higher during the night than during the day. Dexamethasone did not modify the pattern of variation, but induced a significant (P less than 0.001) decrease in PAV. Hematocrit remained stable throughout the study as did osmolality, except at 2000 h, when a significant (P less than 0.001) increase (5 mOsm) on average occurred in every subject. Blood sugar, sodium or chloride did not account for the observed rise in osmolality and no simultaneous change in PAV occurred. A rise in PAV explains, to some extent, the known nocturnal decrease in urine output. Diurnal variations in PAV must be taken into account in clinical investigations involving vasopressin.

No abstract