Diagnosis of primary immunodeficiencies (PIDs) is complex and cumbersome yet important for the clinical management of the disease. Exome sequencing may provide a genetic diagnosis in a significant number of patients in a single genetic test.Alexander Hoischen and Mihai Netea, theme Infectious diseases and global health, and colleagues, published their results in Genome Medicine.
In May 2013, they implemented exome sequencing in routine diagnostics for patients suffering from PIDs. This study reports the clinical utility and diagnostic yield for a heterogeneous group of 254 consecutively referred PID patients from 249 families. For the majority of patients, the clinical diagnosis was based on clinical criteria including rare and/or unusual severe bacterial, viral, or fungal infections, sometimes accompanied by autoimmune manifestations. Functional immune defects were interpreted in the context of aberrant immune cell populations, aberrant antibody levels, or combinations of these factors.
For 62 patients (24%), exome sequencing identified pathogenic variants in well-established PID genes. An exome-wide analysis diagnosed 10 additional patients (4%), providing diagnoses for 72 patients (28%) from 68 families altogether. The genetic diagnosis directly indicated novel treatment options for 25 patients that received a diagnosis (34%).
Exome sequencing as a first-tier test for PIDs granted a diagnosis for 28% of patients. Importantly, molecularly defined diagnoses indicated altered therapeutic options in 34% of cases. In addition, exome sequencing harbors advantages over gene panels as a truly generic test for all genetic diseases, including in silico extension of existing gene lists and re-analysis of existing data.
Related news items
4,8 million euros for prevention of tuberculosis among people with diabetes in Africa16 July 2019
Reinout van Crevel and Lindsey te Brake have received European funding of 4.8 million euros to lead an international consortium to screen thousands of people with diabetes in Uganda and Tanzania for TB, and investigate the effect and costs of 3 months preventive treatment for TB.read more
Handbook of biomarkers and precision medicine a new publication by Alain van Gool12 July 2019
Alain van Gool published a new handbook on biomarkers and applications in (pre)clinical drug development for precision medicine.read more
The real impact of menstrual complaints on work and school productivity8 July 2019
Menstrual period symptoms may be linked to nearly nine days of lost productivity every year, through presenteeism, suggests the largest study of its kind, published in the journal BMJ Open. But the real impact on women and society is underestimated and poorly appreciated, say the researchers.read more
Successful Summer School by CMBI, TML and Human Genetics8 July 2019
CMBI, TML and Human Genetics organized a successful Summer School on 'Integrative X-omics Analyses Empowering Personalized Healthcare'.read more
Walking for science Research by Radboud university medical center and Radboud University during the Vierdaagse (Four Day Marches)5 July 2019
The Vierdaagse is a unique opportunity to conduct research into physical activity and healthy lifestyle.read more