Mutations in collagen 18A1 (COL18A1) and their relevance to the human phenotype

Anais da Academia Brasileira de Ciências

Maria Rita Passos-bueno²  Oscar T. Suzuki²  Lucia M. Armelin-correa²  Andréa L. Sertié²  Flavia I.v. Errera²  Kelly Bagatini²  Fernando Kok²  Katia R.m. Leite¹ 

[1] ,Universidade de São Paulo Instituto de Biociências Centro de Estudos do Genoma HumanoSão Paulo SP ,Brasil

关键词: COL18A1;    collagen XVIII;    Knobloch syndrome;    eye development;    neuronal cell migration;    craniosynostosis;    polymorphisms;    D1437N;    COL18A1;    colágeno XVIII;    síndrome de Knobloch;    desenvolvimento ocular;    migração de célula neuronal;    craniossinostoses;    polimorfismos;    D1437N;   

DOI  :  10.1590/S0001-37652006000100012

来源: SciELO

【 摘 要 】

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 collagen 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.

【 授权许可】

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