Kitiratschky V B D, Nagy D, Zabel T, Zrenner E, Wissinger B, Kohl S, Jägle H
Centre of Ophthalmology, University Eye Hospital, Schleichstr. 12-16, D-72076 Tübingen, Germany.
Br J Ophthalmol. 2008 Aug;92(8):1086-91. doi: 10.1136/bjo.2007.133231.
To describe the detailed phenotypes of a multi-generation family affected by autosomal dominant cone-rod dystrophy (adCRD) and characterised by marked intrafamilial heterogeneity, due to a novel frameshift mutation in the CRX gene.
Six affected and two unaffected family members underwent detailed ophthalmological examination as well as psychophysical and electrophysiological testing. Mutation screening of the CRX gene and segregation analysis were performed in 14 family members from three generations.
Clinical examination of six available mutation carriers showed marked phenotypic heterogeneity, presenting with a reduced cone electroretinogram (ERG) and normal rod ERG in one family branch and a negative ERG in the other as the most striking feature. Genetic screening identified a novel mutation in the CRX gene, c.636delC, that independently segregates with the disease in both branches of the family.
The authors identified a novel disease causing mutation in the CRX gene associated with adCRD. Furthermore, we show here for the first time the coexistence of a reduced cone and a negative ERG component in different individuals of the same family, all affected by the same mutation.
描述一个受常染色体显性遗传视锥-视杆营养不良（adCRD）影响的多代家族的详细表型，该家族因CRX基因中的一个新的移码突变而具有显著的家族内异质性。
对六名患病和两名未患病的家庭成员进行了详细的眼科检查以及心理物理学和电生理学测试。对来自三代的14名家庭成员进行了CRX基因的突变筛查和分离分析。
对六名已知突变携带者的临床检查显示出显著的表型异质性，在一个家族分支中表现为视锥细胞视网膜电图（ERG）降低而视杆细胞ERG正常，而在另一个家族分支中最显著的特征是ERG呈阴性。基因筛查在CRX基因中鉴定出一个新突变，c.636delC，该突变在家族的两个分支中均与疾病独立分离。
作者在与adCRD相关的CRX基因中鉴定出一个新的致病突变。此外，我们首次在此展示了同一家庭中不同个体同时存在视锥细胞反应降低和ERG阴性成分，所有这些个体均受相同突变影响。
