In some patients, their genetic predisposition to keratoconus, that is, polymorphisms in COL4A3 and COL4A4 genes, encoding components of type IV collagen, a major corneal structural protein , and/or mutation in the superoxide dismutase 1 gene  may accelerate the corneal changes.
Strazisar, "Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus," Molecular Vision, vol.
It is caused by mutations in the COL4A3 and/or COL4A4 genes located on chromosome no 2 or the COL4A5 gene on the X chromosome .
Thus, the parents of these siblings must be carriers for Alport syndrome on chromosome # 2, the mutation being either on COL4A3 or COL4A4 or on maybe both.
Three genetic forms of Alport syndrome exist: XLAS, which results from mutations in the COL4A5 gene (85% of cases); ARAS, which is caused by mutations in either the COL4A3 or COL4A4
gene (10-15% of cases); and ADAS, which also is caused by mutations in COL4A3 or COL4A4
and accounts for the remainder of the cases (2,3).
It is encoded by the COL4A4 gene, and mutations of this gene are known to be associated with thin basement membrane nephropathy (TBMN).
For the analysis of the COL4A4 gene, all the exons including splicing sites were amplified by PCR and screened by direct sequencing analysis.
Lmx1b regulates the expression of COL4A3 and COL4A4
genes, as well as NPHS2, the gene encoding for podocin, and its mutated form is associated with abnormal deposition of collagen in the GBM, impaired podocyte differentiation, and development of mesangial and segmental sclerosis.
3 C0L4A3 2q36-q37 COL4A4
2q36-q37 IgA nephropathy IGAN * 6q22-q23 Polycystic kidney PKD1 16p13.
Recently, linkage and mutation analysis in a kindred with TGBM nephropathy has demonstrated a missense mutation in the COL4A4
gene that codes for the [alpha]-4 chain of type IV collagen, resulting in a glycine to glutamic acid substitution.
Still, there are uncommon forms of Alport syndrome linked to mutations in the COL4A4
gene encoding [[alpha].
Autosomal-recessive patients have mutation(s) in either COL4A3 or COL4A4
genes situated on chromosome 2.