Somatic hypermutation defects in two adult hyper immunoglobulin M patients.

ABSTRACT

Hyper immunoglobulin M (HIGM) syndrome is a rare disorder of the immune system with impaired antibody functions. The clinical picture of the patients varies according to the underlying genetic variation. In this study, we identified two novel variants in AID and UNG genes, which are associated with autosomal recessive type HIGM, by targeted next-generation sequencing (NGS) panel. A biallelic 11 base pair deletion (c.278_288delATGTGGCCGAC) in the coding sequence of activation-induced cytidine deaminase (AID) gene was identified in a 36-year-old patient. Biallelic two base pair insertion in exon 7 of uracil nucleoside glycosylase (UNG) gene (c.924_925insGG) was identified in a 40-year-old patient. Both variants were confirmed by Sanger sequencing. HIGM, like many of the other primary immunodeficiencies, is a rare and difficult-to-diagnose entity with heterogeneous clinical phenotypes. It should be suspected in patients with a history of early-onset recurrent respiratory infections, enlarged lymph nodes, and autoimmune disorders. There might be a delay in diagnosis until adulthood especially in subtle cases or if HIGM is not included in the differential diagnosis due lacking of awareness. In this regard, genetic testing with NGS-based diagnostic panels provide a rapid and reasonable tool for the molecular diagnosis of patients with immunodeficiencies and hence, decrease the time to diagnose and prevent infection-related complications associated with increased morbidity and mortality.