Alport syndrome is basically caused by the mutation in COL4A3
, COL4A4, and COL4A5.
Many of the genes belonging to collagen family were found to be upregulated, such as COL141, COL1A1, COL1A2, COL3A1, COL41, COL4A3
, and COL5A1 (Table 2).
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.
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 .
This loss of collagen IV organization is likely to contribute to the phenotype of these lenses as mutations in the COL4A1 gene cause anterior segment defects [58, 59], while mutations in the COL4A3
or COL4A4 genes result in Alport Syndrome in humans, which is associated with anterior and posterior lenticonus, capsular ruptures, and cataracts [59-64].
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.
Interpretation & conclusion: The frequency of COL4A4 mutations in Korean patients with TBMN is low and the other cases may have mutations in other genes like COL4A3
. 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.
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.
For the qRT-PCR of human COL4A3
, ITGA6, and ITGB1, one microgram of total RNA was reverse transcribed into cDNA (ImProm 11 Reverse Transcription System, A3800, Promega, Madison, WI) with Oligo(dT) 15 Primer following manufacturer's instructions.
Mutations in the type IV collagen [[alpha].sub.3] (COL4A3
) gene in autosomal recessive Alport syndrome.