New genetic immunodeficiency identified

22 June 2015

Scientists have identified a new genetic form of immune deficiency linked to mutations in a gene called DOCK2. 

Genetic immunodeficiencies are a group of potentially devastating conditions caused by mutations in specific genes that cause part of the body’s immune system to be absent or not function properly, leaving patients open to a range of severe infections that would not affect healthy individuals. 

Published in the New England Journal of Medicine, the research team report that DOCK2 deficiency may be detectable by newborn screening, and have shown it can be treated effectively with a hematopoietic stem cell transplant.

An author of the study, Luigi Notarengeno of Harvard Medical School, said: “Although congenital immunodeficiencies are rare diseases, the study of these disorders has been essential in identifying key mechanisms governing t he immune system's development and function, and how it helps fight against infections”. 

The international team led by the Boston Children’s Hospital studied five children from different ethnic backgrounds but who had all presented with similar phenotypes i.e. clinical features. The patients’ symptoms indicated a severe but distinctive immunodeficiency, one that left patients susceptible to a broad range of infections but particularly vulnerable to viruses.

Next generation sequencing was carried out on the five patients along with genetic and immunological analysis, to reveal mutations in the gene DOCK2 were the cause of this particular combined immunodeficiency (CIDs). The mutations had an effect on multiple aspects of the patients’ immune system: T-cells and B-cells had impaired ability to move in response to infection-related stimuli, and anti-viral responses were impaired in many cell types. In demonstrating the crucial role of DOCK2 for a healthy functioning immune system, the study will aid understanding of common immune system disorders and the body’s response to infections, according to the researchers.

Three patients were successfully treated with a hematopoietic stem cell transplant, which replaced their defective immune cells with those of a healthy donor. Significantly, the study indicated a new diagnostic target for newborn screening to identify the condition shortly after birth, hopefully in time to limit the potential for life-threatening infection.

Newborn screening for severe combined immunodeficiency (SCID) is offered in many US states, most recently in Virginia. In the UK, systematic population screening for SCID is not offered.

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