Bascom Palmer Eye Institute, University of Miami, 900 NW 17th St, 33136, Miami, FL, USA,
Adv Exp Med Biol. 2014;801:165-70. doi: 10.1007/978-1-4614-3209-8_21.
A single-nucleotide mutation in the gene that encodes DHDDS has been identified by whole exome sequencing as the cause of the non-syndromic recessive retinitis pigmentosa (RP) in a family of Ashkenazi Jewish origin in which three of the four siblings have early onset retinal degeneration. The peripheral retinal degeneration in the affected siblings was evident in the initial examination in 1992 and only one had detectable electroretinogram (ERG) that suggested cone-rod dysfunction. The pigmentary retinal degeneration subsequently progressed rapidly. The identified mutation changes the highly conserved residue Lys42 to Glu, resulting in lower catalytic efficiency. Patterns of plasma transferrin isoelectric focusing gel were normal in all family members, indicating no significant abnormality in protein glycosylation. Dolichols have been shown to influence the fluidity and of the membrane and promote vesicle fusion. Considering that photoreceptor outer segments contain stacks of membrane discs, we believe that the mutation may lead to low dolichol levels in photoreceptor outer segments, resulting in unstable membrane structure that leads to photoreceptor degeneration.
通过全外显子组测序发现，一个编码 DHDDS 的基因中的单核苷酸突变是导致一个具有阿什肯纳兹犹太血统的家族中非综合征性隐性视网膜色素变性（RP）的原因，该家族中的四个兄弟姐妹中有三个患有早期视网膜变性。受影响的兄弟姐妹的周边视网膜变性在 1992 年的初步检查中就已经明显，只有一个的视网膜电图（ERG）可检测到提示视锥-视杆功能障碍。随后，色素性视网膜变性迅速进展。鉴定出的突变将高度保守的残基赖氨酸 42 改变为谷氨酸，导致催化效率降低。所有家族成员的血浆转铁蛋白等电聚焦凝胶模式均正常，表明蛋白质糖基化无明显异常。多萜醇已被证明会影响膜的流动性和促进囊泡融合。由于感光器外段包含膜盘的堆叠，我们认为该突变可能导致感光器外段中的多萜醇水平降低，从而导致不稳定的膜结构，进而导致感光器变性。
