Immunodeficiency Laboratory

This is a preview of subscription content, to check access. Price excludes VAT (USA) Tax calculation will be finalised during checkout. Instant access to the full article PDF. Rent this article via DeepDyve Data Availability Genetic variants reported in this manuscript were submitted and are available at the Leiden Open Variation Database; LOVD (www.lovd.nl/LRBA). References Tangye SG, Al-Herz W, Bousfiha A, et al.

1 INTRODUCTION The knowledge of genetically determined diseases of the immune system has increased tremendously in the last two decades, with almost 500 entities being recognized today.1 Immunodeficiencies (IDs) are heterogeneous diseases characterized by reduced immunocompetence.

Biallelic mutations in LIG4 encoding DNA-ligase 4 cause a rare immunodeficiency syndrome manifesting as infant-onset life-threatening and/or opportunistic infections, skeletal malformations, radiosensitivity and neoplasia. LIG4 is pivotal during DNA repair and during V(D)J recombination as it performs the final DNA-break sealing step. We explored whether monoallelic LIG4 missense mutations may underlie immunodeficiency and autoimmunity with autosomal dominant inheritance.