Mutations in collagen 18A1 (COL18A1) and their relevance to the human phenotype
Mutations in collagen 18A1 (COL18A1) and their relevance to the human phenotype
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DOI：
10.1590/s0001-37652006000100012
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发表时间：
2006-03-01
期刊：
影响因子：
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通讯作者：
Leite, Katia R.M.
中科院分区：
文献类型：
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作者：
Passos-Bueno, Maria Rita;Suzuki, Oscar T.;Leite, Katia R.M.
XVIII 胶原蛋白是一种蛋白聚糖，是基底膜 (BM) 的组成部分。存在三种不同的亚型，仅在 N 末端有所不同，但具有特定的组织和发育表达模式。其 C 末端的裂解产生内皮抑素，一种血管生成抑制剂。在其 N 末端，有一个卷曲基序，似乎与 Wnt 信号传导有关。该基因突变会导致诺布洛赫综合征 (KS)，这是一种常染色体隐性遗传疾病，其特征是玻璃体视网膜和黄斑变性以及枕叶脑膨出。这篇综述讨论了稀有和多态性等位基因对人类表型的影响，表明 XVIII 胶原同种型之一的缺乏足以引起 KS，而导致所有 XVIII 胶原同种型缺乏的无效等位基因与更严重的眼部缺陷相关。这篇综述除了说明 XVIII 胶原蛋白在眼睛发育及其终生结构维持中的功能重要性外，还展示了它在其他组织和器官中的作用，例如神经系统和肾脏。
Collagen XVIII, a proteoglycan, is a component of basement membranes (BMs). There are three distinct isoforms that differ only by their N-terminal, but with a specific pattern of tissue and developmental expression. Cleavage of its C-terminal produces endostatin, an inhibitor of angiogenesis. In its N-terminal, there is a frizzled motif which seems to be involved in Wnt signaling. Mutations in this gene cause Knobloch syndrome (KS), an autosomal recessive disorder characterized by vitreoretinal and macular degeneration and occipital encephalocele. This review discusses the effect of both rare and polymorphic alleles in the human phenotype, showing that deficiency of one of the colla en XVIII isoforms is sufficient to cause KS and that null alleles causing deficiency of all collagen XVIII isoforms are associated with a more severe ocular defect. This review besides illustrating the functional importance of collagen XVIII in eye development and its structure maintenance throughout life, it also shows its role in other tissues and organs, such as nervous system and kidney.