This gene is the most important Alport gene. Mutations account for x-linked Alport syndrome.
The prevalence of COL4A5 mutations is 1:5,000 to 1:10,000. About 0.5% of adult patients on hemodialysis have Alport's syndrome. X-chromosomal Alport's syndrome is the most frequent form (85%).
The Gen COL4A5 coding alpha chain 5 of collagen type IV is about 260kb in size. The gene is localized on x chromosome in head to head orientation with the COL4A6 gene. There are 3 splicing variants known. the constist of 51 or 52 exons. The physiological importance of these variants is not known yet.
Collagen IV alpha 5 is a component of the basement membrane in many organs. However in the glomerular basement membrane, the cornea and cochlea its presence is of most importance as in these places no other alpha chains exist to replace its function. Concllusively, its absence causes specific kidney, eye and hearing symptoms.
Of special immunopathologic diagnostic importance is the presence of collagen IV alpha 5 in the skin and in the Bowman capsule. In the kidney it is easiliy accessible to biopsy, and the absence of the other important Alport collagen IV types 3 and 4 in the Bowman capsule is of importance in differentiating the type of Alport syndrome.
Clinical findings are hereditary nephritis, sensoneural deafness an a plethora of ocular abnormalities. The nephritis starts with erythrocyturia and develops end stage renal disease. The lenticonus anterior is the most pathognomonic ocular abnormality. If in a family females are affected too a autosomal recessive form should be considered. After transplantation the patients might develop Goodpasture like clinical because there might not developed an immuno tollerance.
The different alpha chains of collagen IV form a heterotrimer of variable alpha chain composition. This heterotrimer has the form of a triple helix. Important for the formation of the helical structure is the occurrence of the amino acid glycin at every third position (G-X-Y). The chains are connected by disulfide bounds. This fact is important for the resistance of collagen to collagenases. This alpha chain is a constituent of basement membranes in glomerulum, cochlea and eye.
Early confirmation of diagnosis to provide preemptive therapy. Family counsuling.
Hemizygous male patients suffer from Alport syndrome while heterozygous females show milder symptoms varying from microscopic hematuria to Alport syndrome whose onset is significantly later tha in male patients of the same family.
Clinic | Method | Carrier testing |
Turnaround | 5 days | |
Specimen type | genomic DNA |
Clinic | Method | Massive parallel sequencing |
Turnaround | 25 days | |
Specimen type | genomic DNA |
Clinic | Method | Genomic sequencing of the entire coding region |
Turnaround | 20 days | |
Specimen type | genomic DNA |
Clinic | Method | Multiplex Ligation-Dependent Probe Amplification |
Turnaround | 20 days | |
Specimen type | genomic DNA |
1. |
Nagel M et al. (2005) Novel COL4A5, COL4A4, and COL4A3 mutations in Alport syndrome. |
2. |
Orphanet article Orphanet ID 120722 |
3. |
NCBI article NCBI 1287 |
4. |
OMIM.ORG article Omim 303630 |
5. |
Wikipedia article Wikipedia EN (Collagen,_type_IV,_alpha_5) |