(HealthDay News) — Mutations in the cat eye syndrome chromosome region, candidate 1 (CECR1) gene, encoding adenosine deaminase 2 (ADA2), are associated with vascular and inflammatory phenotypes and with polyarteritis nodosa vasculopathy, according to two studies published online February 19 in the New England Journal of Medicine.

Qing Zhou, PhD, from the National Human Genome Research Institute in Bethesda, MD, and colleagues performed whole-exome sequencing in three unrelated patients with a syndrome of intermittent fevers, early-onset lacunar strokes, and other neurovascular manifestations and their unaffected parents. Candidate-gene sequencing was performed in three patients with a similar phenotype, two young siblings with polyarteritis nodosa, and one patient with small-vessel vasculitis. The researchers identified recessively inherited mutations in CECR1 in all nine patients, which were rare or absent in healthy controls. Six patients were compound heterozygous for eight CECR1 mutations.

Paulina Navon Elkan, MD, from the Shaare Zedek Medical Center in Jerusalem, and colleagues performed exome sequencing in individuals from six families of Georgian Jewish or German ancestry with multiple cases of systemic and cutaneous polyarteritis nodosa. Targeted sequencing was also conducted in additional family members and in unrelated affected individuals of Georgian Jewish and Turkish ancestry. The researchers identified recessive mutations in CECR1, which caused vasculitis in all families. Mutations varied and included a homozygous mutation encoding a Gly47Arg substitution in Georgian Jewish patients, while German patients were compound heterozygous for Arg169Gln and Pro251Leu mutations.

“Recessive loss-of-function mutations of ADA2, a growth factor that is the major extracellular adenosine deaminase, can cause polyarteritis nodosa vasculopathy with highly varied clinical expression,” Elkan and colleagues write.

The Zhou study was funded in part by Sigma Tau Pharmaceuticals.

Abstract – Zhou
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Abstract – Elkan
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