Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical college, Chinese Academy of Medical Sciences, Beijing, China.
MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
Sci Rep. 2017 Aug 1;7(1):7051. doi: 10.1038/s41598-017-07629-3.
Inherited retinal dystrophies (IRDs) are a clinically and genetically heterogeneous group of Mendelian disorders primarily affecting photoreceptor cells. The same IRD-causing variant may lead to different retinal symptoms, demonstrating pleiotropic phenotype traits influenced by both underlying genetic and environmental factors. In the present study, we identified four unrelated IRD families with the HK1 p.E851K variant, which was previously reported to cause autosomal dominant retinitis pigmentosa (RP), and described their detailed clinical phenotypes. Interestingly, we found that in addition to RP, this particular variant can also cause dominant macular dystrophy and cone-rod dystrophy, which primarily affect cone photoreceptors instead of rods. Our results identified pleiotropic effects for an IRD-causing variant and provide more insights into the involvement of a hexokinase in retinal pathogenesis.
遗传性视网膜营养不良（IRDs）是一组临床上和遗传上具有异质性的孟德尔疾病，主要影响光感受器细胞。相同的导致 IRD 的变异可能导致不同的视网膜症状，表现出由潜在的遗传和环境因素共同影响的多效表型特征。在本研究中，我们鉴定了四个不相关的 IRD 家系，其具有先前报道的导致常染色体显性视网膜色素变性（RP）的 HK1 p.E851K 变异，并且描述了它们详细的临床表型。有趣的是，我们发现除了 RP 之外，该特定变异还可导致显性黄斑营养不良和锥杆营养不良，这些疾病主要影响锥光感受器而非杆光感受器。我们的研究结果确定了导致 IRD 的变异的多效性效应，并为六己糖激酶在视网膜发病机制中的作用提供了更多的见解。
