title: Fraser and Ablepharon macrostomia phenotypes: concurrence in one family and association with mutated FRAS1.
abstract: To date, Fraser syndrome (FS) and Ablepharon macrostomia syndrome (AMS) have been considered distinct disorders, but they share strikingly similar patterns of congenital abnormalities, specifically craniofacial anomalies. While recent research has led to the identification of the genes FRAS1 and FREM2 as the cause of FS, the genetic basis of AMS continues to be enigmatic. We report on the concurrence of AMS-like and Fraser phenotypes in a Brazilian family. Both affected sibs were homozygous for a novel splice site mutation in the FRAS1 gene. Extensive studies on mRNA expression indicated that this mutation most likely leads to loss of function as most previously reported FRAS1 mutations associated with FS. We conclude that a phenotype resembling AMS is a rare clinical expression of FS with no obvious genotype-phenotype correlation. However, the molecular basis of "true" AMS which has been reported as a sporadic disorder in all cases but one, and so far with no relation to FS, is probably different and still needs to be further investigated.
authors.affiliation: Perinatal Genetic Program, Department of Medical Genetics, FCM, UNICAMP, Campinas, SP, Brazil.
authors.forename: Denise Pontes
authors.initials: DP
authors.lastname: Cavalcanti
authors.forename: Verena
authors.initials: V
authors.lastname: Matejas
authors.forename: Daniela
authors.initials: D
authors.lastname: Luquetti
authors.forename: Marcos Fernando
authors.initials: MF
authors.lastname: Mello
authors.forename: Martin
authors.initials: M
authors.lastname: Zenker
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008265:Macrostomia / Q000150:complications* / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D050497:Stillbirth
chemical_list: D016326:Extracellular Matrix Proteins; C475145:FRAS1 protein, human