Vilain and McCabe approached the Journal of Clinical Endocrinology and Metabolism, and in 1999 published the first description of the syndrome, which they dubbed IMAGe, an acronym of sorts for the condition's symptoms: intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia and genital anomalies.
Over the next decade, about 20 cases were reported around the world. But the cause of IMAGe syndrome remained a mystery.
Help arrived unexpectedly last year when Vilain received an email from Argentinian physician Dr. Ignacio Bergada, who had unearthed the 1999 journal article. He told Vilain about a large family he was treating in which eight members suffered the same symptoms described in the study. All of the family members agreed to send their DNA samples to UCLA for study.
Vilain realized that he had stumbled across the scientific equivalent of winning the lottery. He assembled a team of UCLA researchers to partner with Bergada and London endocrinologist Dr. John Achermann.
"At last we had enough samples to help us zero in on the gene responsible for the syndrome," Vilain said. "Sequencing technology had also advanced in sophistication over the past two decades, allowing us to quickly analyze the entire family's DNA samples."
Vilain's team performed a linkage study, which identifies disease-related genetic markers passed down from one generation to another. The results steered Vilain to a huge swath of Chromosome 11.
The UCLA Center for Clinical Genomics performed next-generation sequencing, a powerful new technique that enabled the scientists to scour the enormous area in just two weeks and tease out a slender stretch that held the culprit mutation. The team also uncovered the same mutation in the original three cases described by Vilain in 1999.
A word of explanation: Located on 23 pairs of chromosomes, human genes hold the codes for making cellular proteins,
|Contact: Elaine Schmidt|
University of California - Los Angeles Health Sciences