A genetic phenomenon called chromothripsis, or “chromosome shattering,” may have spontaneously cured a patient with WHIM syndrome, an autosomal dominant combined primary immunodeficiency disease caused by mutations of the CXCR4 receptor.
A 58-year-old woman with a history of WHIM contacted the National Institutes of Health to evaluate herself and two of her children, who eventually were diagnosed with WHIM syndrome, which is marked by recurrent infections, warts, and cancer caused by the inability of immune cells, particularly neutrophils, to leave the bone marrow and enter the bloodstream. The patient reported that her symptoms resolved in her 30s, suggesting that she had maintained disease remission for almost 20 years. No other patient has experienced WHIM syndrome remission, according to Dr. David McDermott and his associates.
Chromothripsis, usually a catastrophic event, occurred in a hematopoietic stem cell, deleting the disease allele and more than 150 other genes, repopulating the myeloid but not the lymphoid lineage.
In a competitive mouse bone marrow transplantation experiment, CXCR4 haploinsufficiency was enough to give a strong long-term engraftment advantage of donor bone marrow over bone marrow from either wild type or WHIM syndrome model mice, suggesting a potential mechanism for the patient’s cure, the researchers said.
Read the full article at Cell ( doi: 10.1016/j.cell.2015.01.014 ).