The aim of this study was to investigate a novel pathogenic mutation of FZD4 gene in a Chinese family with familial exudative vitreoretinopathy (FEVR).

Clinical data of 6 cases with autosomal dominant FEVR representing 3 generations of a single family was collected. DNA was extracted from peripheral blood sample taken from 2 FEVR patients and 2 healthy participants. Direct sequencing of 20 000 genes was performed with next-generation sequencing and Sanger sequencing was used to identify the pathogenic gene locus in the FEVR family.

The proband was a 15-year-old female with low vision in both eyes; her best corrected visual acuity (BCVA) were 0.6 (right eye) and 0.5 (left eye). After fundus examination, it showed that there were many vascular branches around the retina, like "willow" shape. After fluorescein fundus angiography, it showed ischemic region. The child had longer limbs, mitral and tricuspid insufficiency, and was suspected of loeys Dietz syndrome. In the family, the BCVA of the proband′s father after laser treatment were 0.2 (right eye) and 0.5 (left eye) with FEVR changes. The proband′s grandparents had cataract, and no abnormality in fundus examination; the proband′s mother and aunt had good visions, and no abnormality in the anterior segments and fundus of her both eyes. After genetic detection of peripheral blood from 4 detector, we found a novel FZD4 pathogenic mutation locus c. 1498delA (p.Thr500fs) mutation (heterozygous frame-shift mutation), which resulted in leucine substitute for threonine in the 500 locus and affected protein′s structure and function. No mutations in FZD4 gene was found in 2 normal participants. Among of 4 tested members, the proband and her mother, were found to carry genes associated with loeys Dietz syndrome, namely TGFβ2/ NM_001135599.3 nucleotide heterozygous variation c. 673G>A, amino acid mutation p. Glu225Lys.

c. 1498delA (p.Thr500fs) was first identified a novel heterozygous frame-shift mutation in the FZD4 gene. It may be the disease-causing mutation in this FEVR family. FZD4 and TGFβ2 genes mutations could exist in one individual.