Mutations in collagen 18A1 and their relevance to the human phenotype.
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.
Departamento de Genética e Biologia Evolutiva, Centro de Estudos do Genoma Humano, Instituto de Biociências, USP, 05508-900 São Paulo, SP, Brazil. passos@ib.usp.br
Maria Rita
MR
Passos-Bueno
Oscar T
OT
Suzuki
Lucia M
LM
Armelin-Correa
Andréa L
AL
Sertié
Flavia I V
FI
Errera
Kelly
K
Bagatini
Fernando
F
Kok
Katia R M
KR
Leite
D000483:Alleles; D043170:Collagen Type XVIII / Q000235:genetics*; D004677:Encephalocele / Q000235:genetics*; D015785:Eye Diseases, Hereditary / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics*; D013577:Syndrome
D043170:Collagen Type XVIII; D020033:Protein Isoforms