Bioethics Blogs

Rare Disease Sleuths Uncover New Clues to Stroke

Drawing of a brain section with an inflamed blood vessel

Caption: A variation in the gene that codes for a key blood vessel enzyme makes children prone to fevers, rash, and strokes.
Credit: Jonathan Bailey, National Human Genome Research Institute, NIH

A medical mystery that began when a 3-year-old girl came to the NIH Clinical Center here in Bethesda, MD, a decade ago has just been solved. The findings not only promise to help children suffering from a devastating rare disease, but to advance our overall understanding of stroke and other blood vessel disorders.

When researchers first met the little girl, they were baffled. She had a most unusual—and unexplained—constellation of symptoms: recurring fevers, rashes, and strokes, which, sadly, had left her severely disabled. Researchers thought the cause probably wasn’t genetic, because none of the girl’s family members were affected, plus they hadn’t seen other children with similar problems. While they searched for clues, they treated the girl with immunosuppressive drugs to reduce blood vessel inflammation and thereby lower the chance of future strokes.

Several years passed, but then two unrelated children with very similar symptoms came to NIH. Like the first little girl, both of these youngsters (a 6-year-old girl and 6-year-old boy) had suffered strokes before the age of 5. The additional patients—along with recent advances in DNA sequencing technology—offered researchers the opportunity to explore more fully whether a gene mutation might be responsible for this puzzling disorder.

So, intramural scientists from seven NIH Institutes and Centers teamed up to sequence and analyze the exomes—the protein-coding part of the genomes—of all three affected children and their unaffected parents.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.