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: Denise Pontes Cavalcanti, Verena Matejas, Daniela Luquetti, Marcos Fernando Mello, Martin Zenker
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 143A Issue 3 Pg. 241-7 (Feb 01 2007) ISSN: 1552-4825 [Print] United States
• PMID: 17163535 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

• Extracellular Matrix Proteins
• FRAS1 protein, human

Topics

• Abnormalities, Multiple (genetics)
• Craniofacial Abnormalities (genetics)
• Extracellular Matrix Proteins (genetics)
• Female
• Humans
• Infant, Newborn
• Macrostomia (complications, genetics)
• Male
• Mutation
• Phenotype
• Stillbirth