Zaremba J, Feil S, Juszko J, Myga W, van Duijnhoven G, Berger W
Institute of Psychiatry and Neurology, Department of Genetics, Warsaw, Poland.
Ophthalmic Genet. 1998 Sep;19(3):157-64. doi: 10.1076/opge.19.3.157.2184.
To describe the phenotypic variability in a Polish Norrie disease (ND) family associated with the missense mutation A63D.
A patient with spared vision from a Polish ND family underwent detailed ophthalmological examinations including slit-lamp biomicroscopy, ultrasound (USG), angiography, Goldmann kinetic visual field, and electroretinography (ERG). Mutation screening was carried out using the single-strand conformation polymorphism (SSCP) technique and subsequent DNA sequencing of the coding part of the ND gene.
A mutation was detected (exon 3, A63D) in a large Polish family with 12 affected males, all but one presenting with classical ND symptoms. In one male, partially preserved vision was observed up to 40 years of age (distance acuity of the right eye 1/50 and left eye 2/50). Slit-lamp examination revealed remnants of a persistent primary vitreous and hyaloid artery. Upon angiography, the retina was vascularized within the posterior pole but not in the periphery. The ERG revealed pathological changes characteristic for chorioretinal degenerations.
Within one family, individuals with identical sequence alterations in the ND gene can show remarkable phenotypic variability of the ocular symptoms. These findings indicate the involvement of additional factors (epigenetic or genetic) in ocular pathogenesis of ND.
描述一个与错义突变A63D相关的波兰诺里病（ND）家系中的表型变异性。
对一名来自波兰ND家系且视力未受影响的患者进行了详细的眼科检查，包括裂隙灯生物显微镜检查、超声检查（USG）、血管造影、戈德曼动态视野检查和视网膜电图（ERG）检查。使用单链构象多态性（SSCP）技术进行突变筛查，并对ND基因的编码部分进行后续DNA测序。
在一个有12名患病男性的波兰大家庭中检测到一个突变（外显子3，A63D），除一人外，所有患者均表现出典型的ND症状。在一名男性中，直到40岁时仍观察到部分视力保留（右眼远视力为1/50，左眼为2/50）。裂隙灯检查发现残留的永存原始玻璃体和玻璃体动脉。血管造影显示，视网膜在后极部有血管形成，但周边部没有。ERG显示出脉络膜视网膜变性的特征性病理变化。
在一个家系中，ND基因序列改变相同的个体可表现出明显的眼部症状表型变异性。这些发现表明，其他因素（表观遗传或遗传）参与了ND的眼部发病机制。
