COL4A4 is one of two genes responsible for autosomal Alport syndrome. Depending on the type of mutation dominant or recessive inheritance is possible. The number of mutated alleles defines the severity of symptoms. Only one allele affected leads to benign hematuria, two alleles Alport syndrome.
The Alport syndrome is responsible for about 0,5-1% of patients on dialysis in Western countries. The autosomal recessive form makes only 15-20% of these.
The gene COL4A4 is located on chromosome 2 (2q36-q37) in a head-to-head position with the COL4A3 gene. Both genes probably use the same promotor. The size is about 160kb. The gene structure consists of 47 exons.
This gene is responsible for autosomal recessive Alport syndrome. That means: in homozygous state a full blown clinical picture of Alport syndrome can be seen that is characterized by progressive nephritis, sensorineural deafness and a plethora of ocular abnormalities. In heterozygous state the clinical picture seems to be equivalent to benign familial hematuria.
The basement membranes of the body mainly consists of collagen type IV. Herein the alpha chains 3, 4 and 5 plays an special role. The highly specialized basement membranes in glomerulum, inner ear and at some ocular locations consists of these chains. Therefore, if one of these chains is disturbed symptoms in these organs are possible.
This investigation is required when the diagnosis of autosomal recessive Alport syndrome has to be confirmed.
The detection of a mutation confirms autosomal recessive Alport syndrome.
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 120720 |
3. |
NCBI article NCBI 1286 |
4. |
OMIM.ORG article Omim 120131 |
5. |
Wikipedia article Wikipedia EN (Collagen,_type_IV,_alpha_4) |