A novel mutation in EFNB1, probably with a dominant negative effect, underlying craniofrontonasal syndrome.
Craniofrontonasal syndrome (CFNS) is an X-linked disorder whose main clinical manifestations include coronal craniosynostosis and frontonasal dysplasia. Very recently, CFNS was shown to be caused by mutations in EFNB1 encoding ephrin-B1, and 20 mutations have been described. We report a Thai woman with CFNS, in whom a novel mutation was discovered: c.685_686insG, in exon 5 of EFNB1. It is the first insertion and the most 3' point mutation in EFNB1 reported to date. The mutation is expected to result in a truncated ephrin-B1 of 230 amino acids, composed of a nearly complete extracellular part of ephrin-B1 with no transmembrane and cytoplasmic domains. This truncated protein might become a soluble form of the ligand, which previously was shown to be able to bind to receptors, but fail to cluster and to activate them--in other words, acting as a dominant negative protein. Nonetheless, further studies to detect the protein are needed to substantiate the hypothesis.
Shotelersuk
Vorasuk
V
Division of Medical Genetics and Metabolism, Department of Pediatrics, Sor Kor Building 11th Floor, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand. vorasuk.s@chula.ac.th
Siriwan
Pichit
P
Ausavarat
Surasawadee
S
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D003398:Craniosynostoses / Q000235:genetics*; D036387:Ephrin-B1; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D009666:Nose / Q000002:abnormalities*; D017354:Point Mutation / Q000235:genetics*; D013577:Syndrome
D002352:Carrier Proteins; C484288:EFNB1 protein, human; D036387:Ephrin-B1