For a long time when possible predisposition to aHUS has been talked about an individual’s GENETIC MUTATION was invariably mentioned. It was said that the components of the complement system CFH, CFI, MCP, C3 and B would each have such a mutation.
So it may be surprise to discover that each complement component has more than one possible mutation and some have over a hundred of these variants. Each of these variants may have different levels of significance when it comes to their impact on an individual experiencing aHUS. Indeed some variants are so common that they could be found in a large number of the general population. So these may have less significance to aHUS ,which is a very rare disease.
Soon after an encounter with aHUS the results of the genetic tests are received, and if one or more of the variants are found the aHUS patient is classified according to the component , or components, that is, or are, at fault . Rarely is the patient told which variant of the faulty complement component they have.
For nearly 10 years , The University College of London has been building up one the biggest and highest regarded databases of aHUS related genetic variants. The database can be seen by clicking here.
In the CFH section 167 variants can be found listed at present ,of which 127 are significant variants associated with aHUS with particular hot spots within 6 of the 20 bits that make up the protien CFH .
So in future clinicians may be talking less about mutations but more about aHUS Sequence Variants and what significance the individual variants may have for the aHUS patient. The UCL database may also be able to gather even more frequency data about individual sequence variants to see how they are distributed among the aHUS patient population.
Who knows where that knowledge might lead as it may do for those with the CFH(C3643C>G,pArg1215Gly) variant?
Or those predisposed considering having children when “aHUS may be triggered by pregnancy” Their significant variants may give clues to their personal risk.
The featured image is that of the Foundation for children with atypical HUS’s string of aHUS pearls. The string is made up of 20 pearls to represent the “bits” or short consensus repeats (SCRs) which make CFH, of which pearls numbers 16 to 20 are of a different colour to highlight where some of significant variants for aHUS might be.