Depending on genetic and nongenetic factors including alterations in gene expression, splice variations, post-translational modifications, and the chain-specific assembly of particular α-chains, different organs can be affected during their development and in the adult life span.
HANAC syndrome Mutations in
COL4A1 exons 24 and 25 are associated with HANAC (
autosomal dominant hereditary
angiopathy with
nephropathy,
aneurysms, and
muscle cramps). It has also been confirmed that mutations in the
COL4A1 gene occur in some patients with
porencephaly and
schizencephaly.
Congenital cataract In humans, a novel mutation of the
COL4A1 gene coding for collagen type IV was found to be associated with autosomal dominant congenital cataract in a Chinese family. This mutation was not found in unaffected family members or in 200 unrelated controls. In this study, sequence analysis confirmed that the Gly782 amino acid residue was highly conserved. This report of a new mutation in the
COL4A1 gene is the first report of a non-syndromic autosomal dominant congenital cataract that highlights an important role for collagen type IV in the physiological and optical properties of the lens. Over the past decade, studies have repeatedly found single-nucleotide
polymorphisms located in the collagen ( COL) 4A1 and
COL4A2 genes to be associated with
cardiovascular disease, and the 13q34 locus harboring these genes is one of the 160 genome-wide significant risk loci for coronary artery disease.
COL4A1 and
COL4A2 encode the α1- and α2-chains of collagen type IV. This is a major component of basement membranes in various tissues including arteries. There are clinical reports linking 13q34 to
coronary artery disease,
atherosclerosis, and artery stiffening from experimental studies based on vascular cells and tissue. Altogether, it was concluded that the pathogenesis of coronary artery disease may be regulated by
COL4A1 and
COL4A2 genes. File:Photomicrograph_showing_Infantile_scurvy_Wellcome_M0002833.jpg|Calcified cartilage, hemorrhage in fibrous marrow, and abnormally thin bone cortex due to scurvy
Collagen hybridizing peptides Collagen, the major structural component of nearly all mammalian tissues, undergoes extensive proteolytic remodeling during developmental states and a variety of life-threatening diseases such as cancer, myocardial infarction, and fibrosis. While degraded collagen could be an important marker of tissue damage, it is difficult to detect and target using conventional tools. As a result, a collagen hybridizing peptide is specifically hybridized to the degraded, unfolded collagen chains, can be used to image degraded collagen and inform tissue remodeling activity in various tissues. Labeled with 5-carboxyfluorescein and biotin, the collagen hybridizing peptide can enable direct localization and quantification of collagen degradation in isolated tissues within pathologic states ranging from osteoarthritis and
myocardial infarction, to
glomerulonephritis and
pulmonary fibrosis, as well as in normal tissues during developmental programs associated with embryonic bone formation and skin aging. Increased glomerular and mesangial deposition of collagen IV occurs in
diabetic nephropathy and increased urinary levels are associated with the extent of renal injury. == See also ==