The genetic basis of invasive meningococcal disease revealed thorough whole exome sequencing

Background Invasive meningococcal disease (IMD) is a rare condition affecting children and young adults due to infection with Neisseria meningitidis, resulting in meningitis or sepsis. Although the majority of the general population is colonized by N. meningitidis, only a small minority go on to develop IMD, suggesting that those that succumb to invasive disease may possess an underlying genetic susceptibility. The notion of a genetic contribution to disease manifestation is supported by the finding that patients with congenital complement deficiencies are susceptible to recurrent IMD, yet these conditions are rare. With the aim of identifying other genetic factors underlying IMD, we carried out whole exome sequencing (WES) of approximately 300 IMD patients from an extensive and well characterized cohort of >2,000 childhood IMD patients. Materials and Methods The WES analysis focused on rare variants (MAF