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Normal vascular development includes the formation and specification of arteries, veins, and intervening capillaries. Vein of Galen malformations (VOGMs) are among the most common and severe neonatal brain arterio-venous malformations, shunting arterial blood into the brain's deep venous system through aberrant direct connections. Exome sequencing of 55 VOGM probands, including 52 parent-offspring trios, revealed enrichment of rare damaging de novo mutations in chromatin modifier genes that play essential roles in brain and vascular development. Other VOGM probands harbored rare inherited damaging mutations in Ephrin signaling genes, including a genome-wide significant mutation burden in EPHB4. Inherited mutations showed incomplete penetrance and variable expressivity, with mutation carriers often exhibiting cutaneous vascular abnormalities, suggesting a two-hit mechanism. The identified mutations collectively account for $30% of studied VOGM cases. These findings provide insight into disease biology and may have clinical implications for risk assessment.

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Recent whole exome sequencing studies in humans have provided novel insight into the importance of the ephrinB2-EphB4-RASA1 signaling axis in cerebrovascular development, corroborating and extending previous work in model systems. Here, we aim to review the human cerebrovascular phenotypes associated with ephrinB2-EphB4-RASA1 mutations, including those recently discovered in Vein of Galen malformation-the most common and severe brain arteriovenous malformation in neonates. We will also discuss emerging paradigms of the molecular and cellular pathophysiology of disease-causing ephrinB2-EphB4-RASA1 mutations, including the potential role of somatic mosaicism. These observations have potential diagnostic and therapeutic implications for patients with rare congenital cerebrovascular diseases and their families.

Pathologist, Leicester Royal Infirmary, Leicester The fatal results of the misuse of thin plastic material, particularly plastic bags, have received wide publicity recently in the medical and lay press both of this country and of the U.S.A. If placed over the face or head the soft plastic may become electrically charged, is readily inhaled into the mouth and nose, where it clings tightly, resists removal, and rapidly produces asphyxia (B.M.J., 1959).Such deaths were thought to be confined to infants and small children, but recently four adult cases of asphyxia due to plastic material about the head have been encountered in unusual circumstances and are reported here.Case 1 On the night before his death this single 23-year-old schoolmlaster stayed late at school, where he was building a canoe.In the morning his body was found wedged in a tall dustbin in one of the closets in the staff lavatory.The body was head down, with the knees bent up to the chest and the ankles extended so that only the buttocks, soles of feet, and hands were visible. On the floor, beside the bin, was a woman's shoe. its fellow lying in the lavatory pan. On a looking-glass shelf above the wash-basins were a box of theatrical grease-paints, other theatrical make-up. and some grease-smeared cotton-wool. A large tin of motor grease was placed below the wash-basin, and elsewhere in the room a rubber kitbag containing pieces of net curtain, more cotton-wool, and scraps of rag was found. Beside the kitbag there was a home-made wooden box, hinged in the middle, 1 ft. (30 cm.) square and obviously intended as a mask, with holes for the neck, eyes, and mouth. The inside ot the mouth-hole was smeared with grease.Great difficulty was experienced in removing the body from the bin, which was 19j in. (49.5 cm.) in diameter and bent slightly oval by the pressure of the body. A small amount of blood from the nose lay in the bottom of the bin.The trunk was dressed in a plastic mackintosh, with a crepe bandage crossing over the chest and the ends wrapped about the neck. Below the mackintosh there were three cotton skirts over a thin rubberized raincoat, and below this again a garment made from a large plastic bag by cutting holes for the arms and neck. About the abdomen and between the legs was a sheet of plastic curtain material with some ejaculated seminal fluid on its inner surface. A pair of false breasts, filled with towelling, were strapped over the chest, and the only male garment was a pair of underpants.A woman's plastic raincap over a rubber bathing-cap covered the head. Net curtaining was tied over the face, which was covered by a " polythene " sheet in which were holes cut for the mouth and eyes. A thick layer of motor grease covered the cheeks and eyes, and, having apparently run, partly occluded the mouth and nose. The face was symmetrically criss-crossed with red and green grease-paint, and blue grease-paint had been smeared over a large area of each cheek.Necropsy.-Death was due to asphyxia.