Posterior Polymorphous Corneal Dystrophy is Associated With TCF8 Gene Mutations in Approximately One-Quarter of Affected Families

Abstract

 

Purpose:

 

To determine whether mutations in the two-handed zinc-finger homeodomain transcription factor gene (TCF8) are associated with the development of posterior polymorphous corneal dystrophy (PPCD).

 

Methods:

 

Screening of TCF8 was performed in 32 affected, unrelated probands, as well as affected and unaffected family members of probands identified with a TCF8 mutation. Any identified sequence variants were screened for in 100 control individuals.

 

Results:

 

Pathogenic mutations were identified in 8 probands: 4 frameshift (c.953_954insA, c.1506dupA, c.1592delA, and c.3012_3013delAG); 3 nonsense (Gln12X, Gln214X, Arg325X); and 1 missense (Met1Arg). Screening of affected and unaffected family members in 5 families demonstrated that each identified mutation segregated with the disease phenotype in each family; 3 probands did not have additional family members available for analysis. None of the eight TCF8 mutations was identified in 200 control chromosomes.

 

Conclusions:

 

TCF8 mutations are associated with posterior polymorphous corneal dystrophy in 25% of affected families.  

 

Keywords: cornea: endothelium • gene screening • genetics