In early 2021, Dr. Michael Ombrello, an investigator at the National Institutes of Health, received a message from doctors at Yale about a patient with a novel genetic mutation—the first of its kind ever seen. A specialist in rare inflammatory and immune disorders, Ombrello was concerned by what first-round genetic tests showed: a disabling mutation in a gene, known as PLCG2, that’s crucial for proper immune functioning. It was hard to discern how the patient, a forty-eight-year-old woman, had survived for so long without serious infections. Even more puzzling was the sudden onset of severe joint pain and swelling she was experiencing after years of excellent health. He decided to bring her to the N.I.H. campus, in Bethesda, Maryland, to study her case first hand.
