Even the basic facts of life taught in elementary school and junior high may not apply to all of us. About one in 3500 people, for example, did not get one copy of each chromosome from mom’s egg and half from dad’s sperm. Some of us got both copies of a chromosome from the same parent, said Fox Chase Cancer Center Researcher David Wiest.
In a paper published this week, Wiest described how this situation cropped up in a medical mystery that would have made for a good episode of House. The patient was a six year old boy with a genetic disease known as Severe Combined Immunodeficiency (SCID). Children with this disease start getting stubborn infections soon after about 6 months of age, when they lose protective antibodies that come from their mothers.
A number of different genetic mutations can cause the problem by preventing the body from making crucial parts of the immune system – B cells and T cells.
Weist is collaborating with Duke University researchers, examining the genetic mutations responsible for the disease. In most cases, people inherit a faulty gene from each parent. In a few others, the faulty gene is on the X chromosome, and in those cases boys will get the disease but not girls, since girls have a second X as a backup.
But in this particular boy, it appeared he got the disease a different way – the faulty gene was on chromosome 1, but only his mother carried the mutation. His father’s chromosome 1 was normal. That was baffling, said Wiest. Sometimes such cases crop up for a mundane reason – that someone else is the biological father (Just the kind of plot twist that makes for good medical dramas).
Luckily, said Wiest, there was no need to deliver uncomfortable news to the parents. The boy had inherited exactly the same mutation on both copies of chromosome 1. A closer look revealed that he had inherited two identical copies of the whole chromosome – both of them from his mother. His dad was his biological father but had somehow managed to pass down only 22 chromosomes to his son rather than the usual 23. So the boy is a little more closely related to his mother than to his father.
Wiest and colleagues published a paper on the boy’s case in this week’s issue of the Proceedings of the National Academy of Sciences. Wiest wants to call attention to the possibility that more cases of genetic disease may come about by such a shuffling error.
The boy may see other health problems down the road, said Weist, because his mother’s chromosome 1 had at least 16 other mutations. That’s not unusual, but normally those would cause no trouble thanks to a normal, back-up copy from the father.
But so far, the prognosis looks good, said Wiest. The boy had a successful bone marrow transplant from his mother and now he’s now doing well. Wiest said it’s a lesson in just how quirky and imperfect the process of reproduction can be. “It’s amazing that children are ever born normal.”
CD45-deficient severe combined immunodeficiency caused by uniparental disomy