Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Alport Syndrome

Alport syndrome is clinically characterized by a hereditary nephritis sensorineural deafness and a plethora of ocular abnormalities. The ultrastructural link between these different manifestations is a basement membrane disorder affecting highly differentiated basement membranes that are present in the glomerulum, organ of Corti and at some ocular localizations.


About 1% of the whole population of dialysis patients suffer from Alport syndrome. It is the most common cause of dialysis among children, however. X-linked Alport syndrome caused by COL4A5 mutations is the most common form. It accounts for 80% of cases. Hence, most of the patients are male. The frequency of heterozygous carriers is 1 in 1000.

Test Strategy

If tumors and inflammatory processes are excluded, a positive family history and a hematuria seems to be sufficient reasons for genetic testing particularly in female. Renal biopsy is recommended in these cases only where family history and clinical symptoms are not typical or mutation screening did not succeed in detecting the relevant mutation.


On the molecular level we find disturbances of collagen type IV caused by mutations in one of the genes COL4A5, COL4A4 or COL4A3.




Nephritic syndrome
CFHR5 Nephropathy
Glomerular basement membrane disorders



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


Gross O et al. (2003) Novel COL4A4 splice defect and in-frame deletion in a large consanguine family as a genetic link between benign familial haematuria and autosomal Alport syndrome.


Jais JP et al. (2003) X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a "European Community Alport Syndrome Concerted Action" study.


Browne G et al. (2004) Retransplantation in Alport post-transplant anti-GBM disease.


Imai E et al. (2004) Perspectives for gene therapy in renal diseases.


Ninichuk V et al. (2005) Delayed chemokine receptor 1 blockade prolongs survival in collagen 4A3-deficient mice with Alport disease.


Ninichuk V et al. (2006) Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice.


Beirowski B et al. (2006) Chronic renal failure and shortened lifespan in COL4A3+/- mice: an animal model for thin basement membrane nephropathy.


Rao VH et al. (2006) Role for macrophage metalloelastase in glomerular basement membrane damage associated with alport syndrome.


Floege J et al. (2006) Bone marrow transplantation rescues Alport mice.


Prodromidi EI et al. (2006) Bone marrow-derived cells contribute to podocyte regeneration and amelioration of renal disease in a mouse model of Alport syndrome.


Alves FR et al. () Revision about hearing loss in the Alport's syndrome, analyzing the clinical, genetic and bio-molecular aspects.


Kashtan CE et al. (2006) Renal transplantation in patients with Alport syndrome.