Genetics and Pathophysiology of Autoinflammatory Disorders

In this study, patients with suspected disorders of inflammation and innate immune system dysregulation will undergo whole exome sequencing. This will involve both family studies (often trios or multiplex families including affected and unaffected individuals) and sporadic cases. The overall objective is to discover rare/novel high-penetrance mutations in genes that have not yet been implicated as the cause of monogenic autoinflammatory diseases. The aim also includes discovery of variants associated with inflammatory disease susceptibility.]]>
Inclusion criteria: individuals who are consented for whole genome/exome sequencing and depict autoinflammatory disease features or who are healthy individuals related to autoinflammatory disease patients. Exclusion criteria: individuals who did not agree to be sequenced. ]]>
This is a natural history study within the intramural research program of the National Human Genome Research Institute (NHGRI), one of the National Institutes of Health (NIH). The study is on-going and has been open to enrollment since 1994. The purpose of this study is to investigate the genetics and pathophysiology of familial Mediterranean fever (FMF) and other related autoinflammatory diseases. FMF is a recessively inherited condition characterized by episodes of fever and serositis or synovitis; some patients also develop systemic amyloidosis. Our laboratory identified the FMF gene and several disease-related mutations, as well as other autoinflammatory disease genes. This study has expanded to include other conditions, sometimes referred to as autoinflammatory syndromes. These syndromes are also characterized by early-onset episodic or sometimes continuous inflammation.]]>