Chapter 13, Problem 26P

WHIM syndrome is a disease of the immune system resulting in warts and frequent infections. The disease is caused by a dominant gain-of-function mutation in a gene on chromosome 2 called CXCR4. A 38-year-old woman suffering with WHIM syndrome her entire life was suddenly and mysteriously cured. Genome analysis of her blood precursor cells (stem cells) revealed that many of these cells had a chromosome 2 that had undergone chromotripsis—a rare (and poorly understood) process where a chromosome is “shattered” into small pieces that are subsequently stitched back together in random order, resulting in many deletions and inversions. Explain how chromotripsis of chromosome 2 in a blood stem cell could have cured the woman of WHIM syndrome.