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.
Passos-Bueno
Maria Rita
MR
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
Suzuki
Oscar T
OT
Armelin-Correa
Lucia M
LM
Sertié
Andréa L
AL
Errera
Flavia I V
FI
Bagatini
Kelly
K
Kok
Fernando
F
Leite
Katia R M
KR
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