Drenser Kimberly A, Dailey Wendelin, Vinekar Anand, Dalal Kunal, Capone Antonio, Trese Michael T
Associated Retinal Consultants, William Beaumont Hospital, 3535 W 13 Mile Rd, No. 344, Royal Oak, MI 48073, USA.
Arch Ophthalmol. 2009 Dec;127(12):1649-54. doi: 10.1001/archophthalmol.2009.322.
To correlate the ophthalmic findings of patients with pediatric vitreoretinopathies with mutations occurring in the FZD4 gene.
A total of 123 patients diagnosed with autosomal-dominant familial exudative vitreoretinopathy (AdFEVR) or retinopathy of prematurity (ROP) and 42 control patients were enrolled in the study. Diagnoses were based on retinal findings at each patient's first examination or during ROP screening. Genomic DNA was isolated and polymerase chain reaction and direct sequencing of the FZD4 gene performed.
FZD4 gene mutations were discovered in 13 of the 123 (10.6%) patients. Nine of the 63 patients with AdFEVR (14.3%) has mutations in the FZD4 gene. Four heterozygous mutations were identified: C117R, C181Y, Q505X, and P33S/P168S. Four of the 60 patients with ROP (6.7%) have a double missense mutation P33S/P168S that was also found in the patients with FEVR. No other FZD4 mutations were found in the patients with ROP. Additionally, patients expressing the double mutation had clinical presentations that overlapped, making it difficult to assign a definitive diagnosis. None of the mutations found in the patients with FEVR or ROP were seen in the control chromosomes.
Mutations occurring in the FZD4 gene affect patients diagnosed with both FEVR and ROP. The clinical picture often overlaps and may require a detailed birth and family history for diagnosis. Genetic testing confirms inherited vitreoretinopathy and helps direct clinical management. Clinical Relevance Patients diagnosed with ROP may have a mutation in the FZD4 gene and display characteristics consistent with FEVR. Analysis of the FZD4 gene should be considered.
将小儿玻璃体视网膜病变患者的眼科检查结果与FZD4基因发生的突变进行关联分析。
本研究共纳入123例诊断为常染色体显性遗传性家族性渗出性玻璃体视网膜病变（AdFEVR）或早产儿视网膜病变（ROP）的患者以及42例对照患者。诊断基于每位患者首次检查时或ROP筛查期间的视网膜检查结果。提取基因组DNA，进行FZD4基因的聚合酶链反应和直接测序。
在123例患者中的13例（10.6%）发现了FZD4基因突变。63例AdFEVR患者中有9例（14.3%）存在FZD4基因突变。鉴定出4种杂合突变：C117R、C181Y、Q505X和P33S/P168S。60例ROP患者中有4例（6.7%）存在双错义突变P33S/P168S，该突变也在FEVR患者中发现。ROP患者中未发现其他FZD4基因突变。此外，表达双突变的患者临床表现有重叠，难以做出明确诊断。在FEVR或ROP患者中发现的突变在对照染色体中均未出现。
FZD4基因发生的突变影响诊断为FEVR和ROP的患者。临床症状常重叠，可能需要详细的出生和家族史以进行诊断。基因检测可确诊遗传性玻璃体视网膜病变并有助于指导临床管理。临床意义诊断为ROP的患者可能存在FZD4基因突变并表现出与FEVR一致的特征。应考虑对FZD4基因进行分析。
