Cecr1 gene

CECR1 stands for the acronym "cat eye syndrome chromosome region, candidate 1" *

The CECR1 gene is located on chromosome 22q11.2 and codes for ADA2, a protein of the adenosine deaminase protein family subfamily. The enzyme ADA2 (adenosine deaminase2) catalyzes the conversion of adenosine to inosine. It is produced by monocytes and regulates cell proliferation and cell differentiation of macrophages and endothelial cells. Mutations in the CECR1 gene lead to a deficient ADA2 with an approximately 4-fold reduced activity of the enzyme. This inhibits the synthesis of ADP (adenosine diphosphate) and other nucleosides (GDP, UDP, CDP). This results in an accumulation of deoxyadenosine, which is increasingly phosphorylated to dATP. The increased concentrations of dATP in turn inhibit ribonucleotide reductase. This also inhibits the synthesis of the other deoxyribonucleotides. The result is a disruption of DNA synthesis with widespread damage to lymphocyte functions and inhibition of lymphocyte proliferation. The result is a severe immunodeficiency

A mutation in the CEDCR1 gene was found in a familial variant of polyarteritis nodosa. In a larger study, 14 of 19 patients were < 10 years old. The pathogenesis was assumed to be that the increased deoxyadenosine levels lead to increased activation of macrophages and prolonged inflammation. Furthermore, an increased tendency to thrombosis and increased endothelial activation were found in this clinical picture. Remarkable is a phenotypic overlap of an ADA2 deficiency with Aicardi-Goutières syndrome (see below familial chilblain lupus) which is caused by a mutation in the SAMHD1 gene and a dysfunction of a nuclease.

*Cat's eye syndrome: The analysis of the genetic material of this disease shows in classical cases a supernumerary chromosome consisting of a fragment of chromosome 22. It is named after the vertical-oval cleft formation (coloboma) on the iris which is present in almost all cases and reminds of the slit pupils of cat eyes.

1. Belot A et al (2014) Mutations in CECR1 associated with a neutrophil signature in peripheral blood. Pediatr Rheumatol Online J 12:44.
2. Hashem H et al (2017) Deficiency of Adenosine Deaminase 2 (DADA2), an Inherited Cause of Polyarteritis Nodosa and a Mimic of Other Systemic Rheumatologic Disorders.
   Curr Rheumatol Rep 19:70.
3. Nanthapisal S et al (2016) Deficiency of adenosine deaminase type 2 (DADA2): A description of phenotype and genotype in 15 cases. Arthritis Rheumatol doi: 10.1002/art.39699.
4. Navon Elkan P et al (2014) Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med 370:921-931.
5. Schepp J et al (2016) Deficiency of Adenosine Deaminase 2 Causes Antibody Deficiency. J Clin Immunol 36:179-186.
6. Van Montfrans JM et al. (2016) Phenotypic variability in patients with ADA2 deficiency due to identical homozygous R169Q mutations Rheumatology (Oxford) 55:902-910.