Alport syndrome is basically caused by the mutation in COL4A3, COL4A4
, and COL4A5.
Endochondral Actin Focal ossification cytoskeleton adhesion VEGFA FGF2 COL11A1 ADAMTS4 FGFR1 COL3A1 PLAT4 TMSB4X COL4A1 COL10A1 GNA13 COL4A2 TGFB2 PDGFA COL4A4
PTHrP FGF1 COL5A1 FGF2 ENAH COL5A2 C4ST1 MSN COL1A1 FGFR1 GSN LAMC2 PDGFRB PDGFRB THBS2 COL1 KRAS CAV2 MRAS ARHGAP5 SOS2 PTEN AKT3 PDGFA PDGFC PGF ITGA2 PDGFRB RAP1B MAPK8 TGF[beta] MAPK signaling signaling Adipogenesis SMURF1 MAPK8 FOXO1A MAPK8 NGFB TRIB3 SKP1 PDGFRB PCK2 NEDD9 RASA2 EGR2 ETS1 SOS2 DDIT3 KLF11 KRAS GADD45A ATF3 MRAS GADD45B FOSB NF1 HIF1A SKIL RAP1B IRS1 SMURF1 DUSP1 MEF2D ZFYVE16 DDIT3 FAS HSPB1 SPOCK IL1A FAS TGFB2 MAP313 ZAK AKT3 MAP3K8 GADD45A Table 2: Genes involved in osteogenesis-related pathways that are downregulated in CYD-treated hMSCs.
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).
It is encoded by the COL4A4
gene, and mutations of this gene are known to be associated with thin basement membrane nephropathy (TBMN).
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.
Still, there are uncommon forms of Alport syndrome linked to mutations in the COL4A4
gene encoding [[alpha].sub.4](IV),15,16 and as such in a patient whose renal biopsy shows EM findings suspicious for Alport syndrome but normal IF staining for [[alpha].sub.3](IV) and [[alpha].sub.5](IV), testing for a COL4A4
mutation may be indicated.
Autosomal-recessive patients have mutation(s) in either COL4A3 or COL4A4
genes situated on chromosome 2.