In a patient with vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome (VAIHS; 615688), Zhou et al. (2014) identified compound heterozygous mutations in the CECR1 gene: a c.506G-A transition in exon 3, resulting in an arg169-to-gln (R169Q) substitution in the PRB domain, and Y453C (607575.0001). Another patient with the disorder was compound heterozygous for R169Q and an intragenic 28-kb deletion. Both mutations occurred at highly conserved residues. Haplotype analysis indicated a founder effect for the R169Q mutation. The R169Q mutation was present in less than 1% of alleles in the 1000 Genomes Project and Exome Variant Server databases; it was not present in the ClinSeq 801 database.
In 4 German sibs with polyarteritis nodosa, Navon Elkan et al. (2014) identified compound heterozygous mutations in the CECR1 gene: R169Q and a c.752C-T transition, resulting in a pro251-to-leu (P251L; 607575.0007) substitution at a highly conserved residue. Each unaffected parent was heterozygous for 1 of the mutations. Among 4,300 European controls, the R169Q variant was found in 7 (0.0008) and the P251L variant was found in 1 (0.0001). Serum ADA2 activity in patients was severely reduced compared to controls. The R169Q protein was barely detectable in transfected cells.
Van Montfrans et al. (2016) identified a homozygous R169Q mutation in the ADA2 gene in 9 patients from 6 unrelated families from the Netherlands with highly variable presentations and manifestations. ADA2 enzyme activity in patients was significantly decreased compared with healthy controls. ADA2 activity levels tended to be lower in patients with stroke compared with patients without stroke.
