707
Two Symptomatic Patients with Atypical Heterozygous Artemis Mutation Along with Other Mutations Including TACI, While Parents with an Isolated Heterozygote Mutation Were Asymptomatic
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Lahari Rampur, MD, Rachel Eisenberg, MD, Jennifer Toh, MD, Arye Rubinstein, MD
Rationale: Most common mutation in Artemis deficiency is the deletion in exons 1-3; phenotypic variation is common with other mutations. Two unrelated gene mutations on different chromosomes encoding immune functions are rarely described.  We report two cases with atypical heterozygous Artemis mutations, one patient with a missense mutation and other unassociated mutations on DCLREC1(Artemis) gene. Second patient with a heterozygous TACI (Chromosome 17) and a heterozygous variant mutation on DCLRE1C (Chromosome 10). Both patients presented with hypogammaglobulinemia and recurrent infections. Parents are asymptomatic with the isolated mutations.

Methods: Case description

Results: A 5 year old female with recurrent infections since age 2 months had low IgG, IgA and IgM, low CD4+ and high CD8+ percent of T cells and failed antibody responses to Pneumococcal polysaccharide and Conjugate vaccines, PPV23 and PCV13 respectively. Genetics revealed a missense mutation on exon 6 of the DCLREC1 gene l: c.457G>A; p.G153R. Other mutations found on DCLREC1 reported as unlikely association.

A 2 year-old male presented with recurrent respiratory infections since age 6 months, had low serum IgG, failed antibody responses to PPV 23 and PCV 13 but normal lymphocyte subsets. Genetics revealed a variant mutation of the DCLRE1C gene of unknown significance: c.251C>G (p.S84C) and a heterozygous missense mutation of TNFRSF13B (TACI) gene associated with CVID type 2: c.310T>C (p.C104R). First patient’s mother with isolated similar heterozygous Artemis mutation and second patient's mother and father with isolated TACI and Artemis mutations respectively are all asymptomatic.

Conclusions: Two Patients with heterozygote Artemis mutations associated with an unrelated gene mutation were immunodeficient while their parents with the isolated mutations were asymptomatic.