Ethanol-Induced Face-Brain Dysmorphology Patterns Are Correlative and Exposure-Stage Dependent 英文参考文献.docVIP

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Ethanol-Induced Face-Brain Dysmorphology Patterns Are Correlative and Exposure-Stage Dependent 英文参考文献.doc

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Ethanol-Induced Face-Brain Dysmorphology Patterns Are Correlative and Exposure-Stage Dependent 英文参考文献

Ethanol-InducedFace-BrainDysmorphologyPatternsAre CorrelativeandExposure-StageDependent RobertJ.Lipinski1*,PeterHammond2,ShonaghK.O’Leary-Moore1,3,JacobJ.Ament1, StephenJ.Pecevich1,YiJiang4,FrancoisBudin3,ScottE.Parnell1,5,MichaelSuttie2,ElizabethA.Godin1, JoshuaL.Everson1,DeborahB.Dehart1,5,IpekOguz3,HunterT.Holloway1,MartinA.Styner3 ,G. AllanJohnson4,KathleenK.Sulik1,5 1TheBowlesCenterforAlcoholStudies,UniversityofNorthCarolina,ChapelHill,NorthCarolina,UnitedStatesofAmerica,2InstituteofChildHealth,UniversityCollege London,London,UnitedKingdom,3DepartmentofPsychiatry,UniversityofNorthCarolina,ChapelHill,NorthCarolina,UnitedStatesofAmerica,4CenterforInVivo Microscopy,DukeUniversity,Durham,NorthCarolina,UnitedStatesofAmerica,5DepartmentofCellandDevelopmentalBiology,UniversityofNorthCarolina,Chapel Hill,NorthCarolina,UnitedStatesofAmerica Abstract Prenatal ethanol exposure is the leading preventable cause of congenital mental disability. Whereas a diagnosis of fetal alcohol syndrome (FAS) requires identification of a specific pattern of craniofacial dysmorphology, most individuals with behavioralandneurologicalsequelaeofheavyprenatalethanolexposuredonotexhibitthesedefiningfacialcharacteristics. Here,anovelintegrationofMRIanddensesurfacemodeling-basedshapeanalysiswasappliedtocharacterizeconcurrent face-brain phenotypes in C57Bl/6J fetuses exposed to ethanol on gestational day (GD)7 or GD8.5. The facial phenotype resultingfromethanolexposuredependeduponstageofinsultandwaspredictiveofuniquepatternsofcorresponding brain abnormalities. Ethanol exposure on GD7 produced a constellation of dysmorphic facial features characteristic of human FAS, including severe midfacial hypoplasia, shortening of the palpebral fissures, an elongated upper lip, and deficient philtrum. In contrast, ethanol exposure on GD8.5 caused mild midfacial hypoplasia and palpebral fissure shortening, a shortened upper lip, and a preserved philtrum. These distinct, stage-specific facial phenotypes were a