Immunodefiency 42D81.4

Autosomal recessive immunodeficiency 42 (IMD42; see also Mendelian susceptibility to mycobacterial diseases) is a rare immunodeficiency syndrome caused by a mutation in the RORC gene. The RORC gene (RFORC stands for "RAR Related Orphan Receptor C") is a protein coding gene located on chromosome 1q21. Two transcript variants encoding different isoforms have been found for this gene.

Immunodeficiency 42 syndrome is characterized by increased susceptibility to mycobacterial and Candida infections beginning in infancy.This RORC mutation causes immunodeficiency that results in severe clinical disease in affected individuals when infected with low virulence mycobacteria, including Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccines (Okada et al.2015)

Okada et al (2015) reported seven patients from three unrelated blood families with immunodeficiency disease characterized by increased susceptibility to mycobacterial and Candida infections. All patients received BCG vaccinations in infancy, and most developed disseminated mycobacterial disease. Six of the 7 patients also had mucocutaneous candidiasis of varying severity. Other features included absence of palpable axillary and cervical lymph nodes and decreased thymus size; some patients had hepatosplenomegaly. Laboratory tests revealed low decreased numbers of T cells and the absence of natural killer T (NKT) type 1 cells and further mucosa-associated invariant T (MAIT) cells. Patients had low levels of innate lymphoid cell type 3 (ILC3). B cells and NK cells were normal.

1. Kurebayashi S et al (2000) Retinoid-related orphan receptor gamma (ROR-gamma) is essential for lymphoid organogenesis and controls apoptosis during thymopoiesis. Proc Nat Acad Sc. 97: 10132-10137.
2. Michelini S et al (2021) Possible Role of the RORC Gene in Primary and Secondary Lymphedema: Review of the Literature and Genetic Study of Two Rare Causative Variants. Lymphat Res Biol 19:129-133.
3. Okada S et al (2015) Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science 349: 606-613.