Yale genetic team diagnoses Turkish boy

A team of Yale researchers have used a new DNA sequencing technique to diagnose a rare disease in a Turkish infant.

In May, doctors from the Istanbul Faculty of Medicine asked Sterling Professor Richard Lifton, Yale Sequencing Center Director Shrikant Mane and post-doctoral fellow Murim Choi to use whole exome sequencing, which analyzes the genes that code for proteins, to figure out why a five-month-old Turkish boy was severely dehydrated. Their finding — that the boy has a rare birth defect — was published in the Oct. 19 online issue of the Proceedings of the National Academy of Sciences, a weekly journal.

The baby’s doctors suspected the infant had Bartter syndrome, which prevents the kidneys from reabsorbing salt, potassium and water. But when the baby did not respond to potassium supplements and other treatments, they consulted Lifton’s lab, which specialized in genetic kidney disorders.

Over 10 days, Lifton and his team analyzed the baby’s blood samples, which were flown over from Istanbul, and compared its DNA to a model of the human genome. They found the baby had none of the genes for Bartter syndrome. Instead, they found the baby had congenital chloride diarrhea, a rare condition that also causes severe dehydration.

“We found that the disease-causing mutation was not one that was on the ‘suspect list,’ ” Lifton wrote in an e-mail Wednesday. “This represents the utility [of genetic analysis] in establishing an unexpected diagnosis.”

While genetic sequencing has been used by researchers to make diagnoses, older technologies looked at much larger portions of the genome. Because whole exome sequencing analyzes only the 1 percent of the human genome that codes for proteins, the process is much faster and is 10 to 20 times less costly than sequencing the entire genome, Lifton said.

A healthy person has about 20,000 mutations, most of which are harmless. Congenital chloride diarrhea, however, is a rare recessive gene mutation, which means that both parents carried the gene. Because the baby’s parents were first cousins, the probability that such a mutation would occur was much higher.

Mane said whole exome sequencing should become widespread within a few years. Eventually, he said, genetic analysis could give rise to personalized medicine.

“With this kind of technology we can tailor-make the medicines that are most effective for each patient,” Mane said. “[This technology] will revolutionize how medicine works.”

Genetic analysis could also help doctors and patients check diagnoses, Choi said.

“There might be a big surge of instances where if you’re not sure of your diagnosis, or if you want to see what gene is causing a certain disease, you can simply sequence your genes and find an answer,” he said.

Comments

  • Complete the story!

    And, will they be able to help the boy or is the human life involved an abstraction in face of the marvels of science?

  • SOM

    The defect was not a mutation, at least not in the patient. It was a recessive variant passed down by both parents, an occurrence which was made more likely because of the consanguineous marriage. The only certain mutation is the SNP within the linkage block that was otherwise identical by descent.