Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Collagen type IV, alpha 4

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.

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 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.

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:

Clinic Method Carrier testing
Turnaround 5
Specimen type genomic DNA
Clinic Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 20
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 20
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25
Specimen type genomic DNA

Related Diseases:

Alport Syndrome
COL4A3
COL4A4
COL4A5

References:

1.

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

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Update: Sept. 26, 2018