Cerebro-retinal angiopathies COL4A1 - Theoretical and practical information currently available

Hereditary cerebro-retinal angiopathies with mutation of the COL4A1 gene are one of the rare causes identified thus far of hereditary disease of the small cerebral arteries, with cerebral haemorrhage and leukoencephalopathy. Other clinical signs may be associated with this, either in the patient himself or in one of his relatives, including:

  • infantile neonatal hemiplegia
  • and/or retinal arteriolar tortuosity
  • and/or abnormalities in the eye (cataract, glaucoma)
  • and/or kidney damage (hematuria).

Transmission is autosomic dominant. There are cases that appear to be sporadic because of the existence of new mutations in a patient, neither of whose parents carried the mutation.
The diagnosis of certainty is molecular. The gene implicated is COL4A1, situated on the long arm of chromosome 13. It consists of 52 exons and codes for the alpha chain of Type IV collagen, an essential constituant of basal membranes, especially the basal membranes of blood vessels.
To date, only 9 mutations have been described in humans on gene COL4A1. Eight of them affect a glycine within the repeated motifs Gly-X-Y in the triple helix domain (two alpha1 chains and one alpha2 chain).
Because of the recent discovery of the implication of this gene, the spectrum of the mutations and the genotype/phenotype correlations have not yet been established. Indications for the prescription of these tests remain to be defined.

To meet the demand of clinicians faced with suspected hereditary cerebro-retinal angiopathies with mutation of the COL4A1 gene, our laboratory has introduced the sequencing of the 52 exons coding for the entire gene as a routine diagnosis.

However, before any blood sample is taken, the case must be discussed (contact E. Tournier Lasserve, Tel: 01 49 95 86 23).