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).
Past medical history includes adulthood onset, autosomal recessive type AS, due to a missense mutation in the COL4A3
gene, with development of severe renal insufficiency, hypertension, anterior lenticonus and mild sensorineural deafness for 4 years.
Screening of the COL4A3 gene and finding a novel causative gene for TBMN will help clarify the pathogenesis of this disorder and perhaps for distinguishing TBMN from Alport syndrome.
Heterozygous mutations have been shown to occur in COL4A3 and COL4A4, which are important parts of the framework for the basement membrane (8-15).
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.
Real-time PCR was performed with TaqMan Gene Expression Master Mix (4369016, Applied Biosystems, Foster City, CA) and target gene primers: COL4A3
(4331182, Hs01022542_m1, Applied Biosystems), ITGA6 (4331182, Hs01041011_m1, Applied Biosystems), and ITGB1 (4331182, Hs00559595_m1, Applied Biosystems).
Structure of the human type IV collagen gene COL4A3
and mutations in autosomal Alport syndrome.
Autosomal-recessive patients have mutation(s) in either COL4A3
or COL4A4 genes situated on chromosome 2.