title: Clinical and genetic aspects of craniofrontonasal syndrome: towards resolving a genetic paradox.
abstract: Craniofrontonasal syndrome (CFNS) is characterized by body asymmetry, midline defects, skeletal abnormalities, and dermatological abnormalities. It is a very peculiar X-linked syndrome because females are affected whereas male carriers show no or only mild abnormalities. Using a combination of positional approach and candidate gene strategy the EFNB1 gene in Xq12 was identified as the major causative gene of this condition. So far, 46 EFNB1 mutations have been detected in CFNS patients. The majority of the mutations lead to premature termination codons. Because the encoded protein ephrin-B1 is involved in migration of neural crest cells we propose that CFNS is a novel type of neurocrestopathy. The absent or mild phenotype in male carriers may be explained by the promiscuity of the ephrin ligand/receptor system. The more severe manifestation in females may be explained by cellular interference that is caused by the combination of ephrin ligand/receptor promiscuity and the consequences of random X inactivation in distinct cellular compartments.
authors.affiliation: Institut für Humangenetik, Otto-von-Guericke-Universität, Leipziger Str. 44, D-39120 Magdeburg, Germany. peter.wieacker@medizin.uni-magdeburg.de
authors.forename: Peter
authors.initials: P
authors.lastname: Wieacker
authors.forename: Ilse
authors.initials: I
authors.lastname: Wieland
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009666:Nose / Q000002:abnormalities*; D036081:Receptors, Eph Family / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012886:Skull / Q000002:abnormalities*; D013577:Syndrome
chemical_list: D036081:Receptors, Eph Family