Wu Wei-Chi, Drenser Kimberly, Trese Michael, Capone Antonio, Dailey Wendy
Associated Retinal Consultants, William Beaumont Hospital, 3535 W. 13 Mile Road, Royal Oak, MI 48073, USA.
Arch Ophthalmol. 2007 Feb;125(2):225-30. doi: 10.1001/archopht.125.2.225.
To correlate the ophthalmic findings of patients with pediatric vitreoretinopathies with mutations occurring in the Norrie disease gene (NDP).
One hundred nine subjects with diverse pediatric vitreoretinopathies and 54 control subjects were enrolled in the study. Diagnoses were based on retinal findings at each patient's first examination. Samples of DNA from each patient underwent polymerase chain reaction amplification and direct sequencing of the NDP gene.
Eleven male patients expressing mutations in the NDP gene were identified in the test group, whereas the controls demonstrated wild-type NDP. All patients diagnosed as having Norrie disease had mutations in the NDP gene. Four of the patients with Norrie disease had mutations involving a cysteine residue in the cysteine-knot motif. Four patients diagnosed as having familial exudative vitreoretinopathy were found to have noncysteine mutations. One patient with retinopathy of prematurity had a 14-base deletion in the 5' untranslated region (exon 1), and 1 patient with bilateral persistent fetal vasculature syndrome expressed a noncysteine mutation in the second exon.
Mutations disrupting the cysteine-knot motif corresponded to severe retinal dysgenesis, whereas patients with noncysteine mutations had varying degrees of avascular peripheral retina, extraretinal vasculature, and subretinal exudate.
Patients exhibiting severe retinal dysgenesis should be suspected of carrying a mutation that disrupts the cysteine-knot motif in the NDP gene.
将小儿玻璃体视网膜病变患者的眼科检查结果与诺里病基因(NDP)中的突变进行关联。
109例患有不同小儿玻璃体视网膜病变的受试者和54例对照受试者纳入本研究。诊断基于每位患者首次检查时的视网膜检查结果。对每位患者的DNA样本进行聚合酶链反应扩增和NDP基因直接测序。
在测试组中鉴定出11例表达NDP基因突变的男性患者,而对照组显示为野生型NDP。所有被诊断为诺里病的患者NDP基因均有突变。4例诺里病患者的突变涉及半胱氨酸结基序中的一个半胱氨酸残基。4例被诊断为家族性渗出性玻璃体视网膜病变的患者被发现有非半胱氨酸突变。1例早产儿视网膜病变患者在5'非翻译区(外显子1)有14个碱基的缺失,1例双侧永存原始玻璃体增生症患者在外显子2中表达了一个非半胱氨酸突变。
破坏半胱氨酸结基序的突变与严重的视网膜发育异常相对应,而非半胱氨酸突变的患者有不同程度的周边视网膜无血管、视网膜外血管和视网膜下渗出。
表现出严重视网膜发育异常的患者应怀疑携带破坏NDP基因中半胱氨酸结基序的突变。