Update on CECR1 molecular diagnostics: new mutations in the deficiency of ADA2 (DADA2) and the North American polyarteritis nodosa (PAN) cohort

Results 14/19 patients were homozygous or compound heterozygous for rare or novel missense mutations in the coding region of CECR1. In 5 patients, we have detected only one likely disease-associated mutation; further analysis is necessary to identify a possible genomic deletion or a second mutation in the non-coding region of CECR1. We have found three rare missense mutations that were not previously associated with DADA2: A357T, G358R, and L249P. More importantly, we have identified four novel mutations that cause DADA2: T129P, K55del, N370K and N423K. The R169Q mutation is a founder mutation in the Dutch population, while the G47R mutation is a founder mutation in the Middle Eastern and Pakistani populations. In the PAN cohort, we identified 6/92 patients with mutations in CECR1. Three patients carry biallelic homozygous or compound heterozygous mutations, and three patients are carriers for a single mutation in CECR1. Four rare variants are reported in Ensemble or ExAC, but they have not been previously associated with PAN: P106S, F355L, V349I, and T65M. We have identified one novel mutation in the cohort with PAN: E328K.