Academic
Publications
Missense Mutations in TCF8 Cause Late-Onset Fuchs Corneal Dystrophy and Interact with FCD4 on Chromosome 9p

Missense Mutations in TCF8 Cause Late-Onset Fuchs Corneal Dystrophy and Interact with FCD4 on Chromosome 9p,10.1016/j.ajhg.2009.12.001,American Journa

Missense Mutations in TCF8 Cause Late-Onset Fuchs Corneal Dystrophy and Interact with FCD4 on Chromosome 9p   (Citations: 4)
BibTex | RIS | RefWorks Download
S. Amer Riazuddin, Norann A. Zaghloul, Amr Al-Saif, Lisa Davey, Bill H. Diplas, Danielle N. Meadows, Allen O. Eghrari, Mollie A. Minear, Yi-Ju Li, Gordon K. Klintworth, Natalie Afshari, Simon G. Gregoryhttp://academic.research.microsoft.com/io.ashx?type=5&id=6354693&selfId1=0&selfId2=0&maxNumber=12&query=
Fuchs corneal dystrophy (FCD) is a degenerative genetic disorder of the corneal endothelium that represents one of the most common causes of corneal transplantation in the United States. Despite its high prevalence (4% over the age of 40), the underlying genetic basis of FCD is largely unknown. Here we report missense mutations in TCF8, a transcription factor whose haploinsufficiency causes posterior polymorphous corneal dystrophy (PPCD), in a cohort of late-onset FCD patients. In contrast to PPCD-causing mutations, all of which are null, FCD-associated mutations encode rare missense changes suggested to cause loss of function by an in vivo complementation assay. Importantly, segregation of a recurring p.Q840P mutation in a large, multigenerational FCD pedigree showed this allele to be sufficient but not necessary for pathogenesis. Execution of a genome-wide scan conditioned for the presence of the 840P allele identified an addi- tional late-onset FCD locus on chromosome 9p, whereas haplotype analysis indicated that the presence of the TCF8 allele and the disease haplotype on 9p leads to a severe FCD manifestation with poor prognosis. Our data suggest that PPCD and FCD are allelic vari- ants of the same disease continuum and that genetic interaction between genes that cause corneal dystrophies can modulate the expres- sivity of the phenotype.
Journal: American Journal of Human Genetics - AMER J HUM GENET , vol. 86, no. 1, pp. 45-53, 2010
Cumulative Annual
View Publication
The following links allow you to view full publications. These links are maintained by other sources not affiliated with Microsoft Academic Search.
Sort by: