Brézin Antoine P, Nedelec Brigitte, Barjol Amandine, Rothschild Pierre-Raphael, Delpech Marc, Valleix Sophie
Université Paris-Descartes, Centre Cochin Ambulatoire d’Ophtalmologie, Assistance Publique Hôpitaux de Paris, France.
Mol Vis. 2011;17:1669-78. Epub 2011 Jun 22.
To detail the highly variable ocular phenotypes of a French family affected with an autosomal dominantly inherited vitreoretinopathy and to identify the disease gene.
Sixteen family members with ten affected individuals underwent detailed ophthalmic evaluation. Genetic linkage analysis and gene screening were undertaken for genes known to be involved in degenerative and exudative vitreoretinopathies. Qualitative reverse transcriptase-PCR analysis of the versiscan (VCAN) transcripts was performed after mutation detection in the VCAN gene.
The first index patient of this French family was referred to us because of a chronic uveitis since infancy; this uveitis was associated with exudative retinal detachment in the context of a severe uncharacterized familial vitreoretinopathy. Genetic linkage was obtained to the VCAN locus, and we further identified a new pathogenic mutation at the highly conserved splice acceptor site in intron 7 of the VCAN gene (c.4004-2A>T), which produced aberrantly spliced VCAN transcripts.
Extensive molecular investigation allowed us to classify this familial vitreoretinopathy as Wagner syndrome. This study illustrates the need to confirm clinical diagnosis by molecular genetic testing and adds new ocular phenotypes to the Wagner syndrome, such as vascular and inflammatory features.
详细描述一个患有常染色体显性遗传性玻璃体视网膜病变的法国家庭的高度可变的眼部表型，并确定致病基因。
对16名家庭成员（其中10人患病）进行了详细的眼科评估。对已知与退行性和渗出性玻璃体视网膜病变相关的基因进行了遗传连锁分析和基因筛查。在检测到VCAN基因的突变后，对versiscan（VCAN）转录本进行了定性逆转录聚合酶链反应分析。
这个法国家庭的首例索引患者因自婴儿期起就患有慢性葡萄膜炎而被转诊至我们这里；这种葡萄膜炎与严重的、未明确特征的家族性玻璃体视网膜病变背景下的渗出性视网膜脱离有关。获得了与VCAN基因座的遗传连锁，并且我们进一步在VCAN基因第7内含子的高度保守的剪接受体位点鉴定出一个新的致病突变（c.4004-2A>T），该突变产生异常剪接的VCAN转录本。
广泛的分子研究使我们能够将这种家族性玻璃体视网膜病变归类为瓦格纳综合征。本研究说明了通过分子基因检测来确认临床诊断的必要性，并为瓦格纳综合征增加了新的眼部表型，如血管和炎症特征。
