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Mutation compromising immunity links two diseases

Published online 9 July 2015

A mutation in a single gene may be responsible for two previously unlinked diseases. 

Sedeer El-Showk

Researchers have discovered that mutation of a single gene underlies susceptibility to two unrelated diseases. The finding reveals an unexpected link between infections by Candida fungi and Mycobacterium species, including the bacteria behind tuberculosis.

The researchers used high-throughput sequencing to identify mutations in seven patients suffering from both candidiasis and mycobacterial infection, both of which are more common in people with a weaker immune system. “Patients with mycobacteriosis and candidiasis are exceedingly rare, and recognition that these patients had a novel primary immunodeficiency required astute physicians,” says Janet Markle, a lead author of the study. Saleh Al-Muhsen’s team at King Saud University played a key role by identifying three patients from a Saudi family.

The analysis revealed mutations in only one gene, RORC, in the genomic interval associated with the diseases. Previous work in mice showed that RORC is required for T cells to produce interleukin IL-17A/F, which is important for protection against Candida albicans. However, the new results demonstrate that RORC is also needed by another type of T cell in order to produce the interferon IFN-γ in response to exposure to mycobacteria. 

“This work will lead to deeper investigations of several cell types that are affected in RORC mutant patients, some, or all, of which may be important,” says Markle.


Okada, S. et al. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science 10.1126/science.aaa4282 (2015).