Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type XVIII collagen is a component of basement membranes, and expressed prominently in the eye, blood vessels, liver, and the central nervous system. Homozygous mutations in COL18A1 lead to Knobloch Syndrome, characterized by ocular defects and occipital encephalocele. However, relatively little has been described on the role of type XVIII collagen in development, and nothing is known about the regulation of its tissue-specific expression pattern. We have used zebrafish transgenesis to identify and characterize cis-regulatory sequences controlling expression of the human gene. Candidate enhancers were selected from non-coding sequence associated with COL18A1 based on sequence conservation among mammals. Although these displayed no overt conservation with orthologous zebrafish sequences, four regions nonetheless acted as tissue-specific transcriptional enhancers in the zebrafish embryo, and together recapitulated the major aspects of col18a1 expression. Additional post-hoc computational analysis on positive enhancer sequences revealed alignments between mammalian and teleost sequences, which we hypothesize predict the corresponding zebrafish enhancers; for one of these, we demonstrate functional overlap with the orthologous human enhancer sequence. Our results provide important insight into the biological function and regulation of COL18A1, and point to additional sequences that may contribute to complex diseases involving COL18A1. More generally, we show that combining functional data with targeted analyses for phylogenetic conservation can reveal conserved cis-regulatory elements in the large number of cases where computational alignment alone falls short.
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PMID:Functionally conserved cis-regulatory elements of COL18A1 identified through zebrafish transgenesis. 1989 2

Knobloch Syndrome (KS) is a rare autosomal recessive hereditary disease. Despite its clinical heterogeneity, it is characterized by vitreoretinal degeneration and high myopia, with or without occipital skull defects. It is caused by mutations in the COL18A1 gene, which codifies for collagen XVIII, present in retina and vascular endothelium. Since the first description of the disease by doctors Knobloch and Layer in 1972, over 100 cases and 20 pathogenic or likely pathogenic mutations have been reported. We present the case of a child born from a consanguineous couple in Chile with congenital high myopia and dysmorphisms without an occipital skull defect. Whole exome sequencing analysis revealed an inherited homozygous variant in COL18A1, c.4224_4225delinsC, p.Pro1411Leufs*35.
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PMID:Knobloch syndrome in a patient from Chile. 3270 Apr 29