Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families
Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families
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DOI：
10.1038/sj.ejhg.5201817
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发表时间：
2007-06-01
影响因子：
5.2
通讯作者：
Golovleva, Irina
中科院分区：
文献类型：
--
作者：
Kohn, Linda;Kadzhaev, Konstantin;Golovleva, Irina
常染色体显性视锥细胞营养不良 (CORD5) (MIM 600977) 是一种主要影响视锥光感受器的罕见疾病。在这里，我们将之前映射到 17p13 的 CORD5 基因座从 27cM 改进到 14.3cM，并在两个瑞典家族的磷脂酰肌醇转移 (PIT) 膜相关蛋白 (PITPNM3) (MIM 608921) 中鉴定出错义突变 Q626H。 PITPNM3 被称为果蝇视网膜变性 B (rdgB) 的人类同源物，缺乏磷脂运输、光感受器膜更新和提供光视网膜电图 (ERG) 响应所需的 N 端 PIT 结构域。在我们的研究中，导致 CORD5 的突变位于与非受体蛋白酪氨酸激酶成员 PYK2 相互作用的 C 端区域。我们对果蝇 rdgB 人类同源物中第一个突变的发现表明了 PITPNM3 在哺乳动物光转导中的新途径和潜在的重要作用。
Autosomal dominant cone dystrophy (CORD5) (MIM 600977) is a rare disease predominantly affecting cone photoreceptors. Here we refine the CORD5 locus previously mapped to 17p13 from 27 to 14.3cM and identified a missense mutation, Q626H in the phosphatidylinositol transfer ( PIT) membrane-associated protein (PITPNM3) ( MIM 608921) in two Swedish families. PITPNM3, known as a human homologue of the Drosophila retinal degeneration B ( rdgB), lacks the N-terminal PIT domain needed for transport of phospholipids, renewal of photoreceptors membrane and providing the electroretinogram ( ERG) response to light. In our study, the mutation causing CORD5 is located in the C-terminal region interacting with a member of nonreceptor protein tyrosine kinases, PYK2. Our finding on the first mutation in the human homologue of Drosophila rdgB indicates novel pathways and a potential important role of the PITPNM3 in mammalian phototransduction.