Purpose: Autosomal dominant (familial) exudative vitreoretinopathy (adEVR) is a rare, congenital disease of the retinal vascular system, which may lead to blindness in severely affected eyes. One of the causative disease genes is located on chromosome 11q13-q23 and codes for "frizzled-4" (FZD4), a protein involved in vascular differentiation.
Method: Examination of two families with adEVR over six and four generations and FZD4 mutation analysis.
Results: In family I, 18 examined affected members exhibited a heterozygous missense mutation (p.G492R) in the FZD4 gene. In family II, four examined family members were affected and carried a heterozygous deletion of five nucleotides (c.1286del5). Both mutations are novel and showed 100% penetrance and variable expressivity.
Conclusions: With detection of the "family-specific" FZD4 gene mutation, carriers amongst offspring of affected family members can be identified at an early time. The complete penetrance of FZD4 mutations may justify abandoning repeated examinations of offspring of affected family members, if no mutations were detected in FZD4.