Collagen type IV, alpha 3

COL4A3 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.

Epidemiology

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.

Gene Structure

The gene COL4A3 is located on chromosome 2 (2q36-q37) in a head-to-head position with the gene COL4A4 . Both genes probably use the same promotor. The size is about 150kb. There exists 3 splice variants with 51, 49 and 48 exons.

Phenotype

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.

Pathology

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.

Test Strategy

This investigation is required when the diagnosis of autosomal recessive Alport syndrome has to be confirmed.

Interpretation

The detection of a mutation confirms autosomal recessive Alport syndrome.

Genetests:

Related Diseases:

Alport Syndrome
	COL4A3
	COL4A4
	COL4A5

Goodpasture syndrome
	COL4A3
	COL4A3BP
	COL4A5

References:

1.	Nagel M et al. (2005) Novel COL4A5, COL4A4, and COL4A3 mutations in Alport syndrome.

2.	Orphanet article Orphanet ID 120718

3.	NCBI article NCBI 1285

4.	OMIM.ORG article Omim 120070

5.	Wikipedia article Wikipedia EN (Collagen,_type_IV,_alpha_3)