Researchers have announced their identification of a specific gene mutation that can lead to atypical hemolytic uremic syndrome (aHUS). This gene is called DGKE and it is not a part of the complement system. This system includes over 20 proteins that are all involved in the bodies immune response.
This means that contrary to previous understanding, the activation of this system is not always necessary for an aHUS diagnosis.
This study has been published in BMC Medical Genetics.
The Mutation
The mutation this group discovered has been named c.942C > G or p.Asn314Lys. It is the first of this type of variant to be discovered to cause aHUS, although other DGKE mutations have previously been noted.
The DGKE protein does have strong pro-clotting effects, although it in and of itself is an unusual cause of the disease.
The team compared the mutated protein and the wild-type protein using a prediction software package as well as a 3-D structure analysis. Although they note that further research is necessary, this finding is important for understanding the genetic manifestations of aHUS.
The Case
This investigation was completed by a team at Iran University. A 19 year old patient was first suspected of having the condition at 7 and a half months. However, her complement factors all within a normal range. The team knew she had a DGKE mutation but the specific mutation was unknown.
The patient had kidney damage and anemia, as well as low platelets. These are all signs of aHUS.
Her parents did not have the condition however her older sister did. Sadly, her sister passed away at just 7 months old due to disease complications.
The entire family had whole exome sequencing done to determine who was carrying an aHUS mutation. Her parents did not have a DGKE gene mutation but the 19 year old did. These were homozygous mutations which means that she had one copy of the gene inherited from each parent.
This finding has important implications for the study of this condition, and the diagnosis of future patients.
You can read more about this study here.
