In addition to studying the more common neurodegenerative conditions like Alzheimer’s or Parkinson’s disease, we also devote a substantial portion of our time working on more rare conditions.
While studying a Portuguese family presenting with Sneddon’s syndrome, a rare and progressive, noninflammatory arteriopathy, we have identified mutations in the CECR1 gene. This gene has just been shown to be the cause of a novel syndrome called ADA2 deficiency (for the NIH press release see here and for the original publication here). The initial description of the phenotype associated with the gene included a very early onset of the disease (the proband showed symptoms at age 3), fevers, skin rash and strokes that left the patient severely disabled.
The family we studied included a total of nine siblings and showed an even more complex phenotype, with livedo racemosa, leg ulcerations, and intermittent fevers that fluctuated with the seasons. Four of the siblings also had ischemic strokes, hemorrhagic strokes, or both during early adulthood.
By using the most state-of-the-art genetic technologies, we have been able to identify a novel compound heterozygous mutation in the CECR1 gene as the cause of the phenotype in this large family.
These results are very important. They show that this gene is involved in a wider range of phenotypes and symptoms than what was originally thought, suggesting that it may be a more frequent cause of disease.
This is a common theme that we have been seeing as we continue to use these novel methods that look at a person’s genome in an unbiased manner. We have recently published this concept in a scientific paper in HMG.
Our work on CECR1 was published today in The New England Journal of Medicine.