犹他大学奖励6美元.4 M from NIH 从长椅到摇篮 initiative to research causes of neurodevelopmental disorders in children born with congenital heart defects
盐湖城——30年前, being born with a severe heart defect was practically a death sentence. But as advances in medicine have given rise to generations of survivors, it's emerging that over half have behavioral problems and difficulty keeping up academically. Two groups from the University of Utah School of Medicine were awarded $6.4 million from the National Institutes of Health's 从长椅到摇篮 initiative to identify causes of these disabilities, and ways to intervene.
It's estimated that up to 80 percent of these neurodevelopmental disabilities cases remain unexplained. While it was first assumed that the symptoms were side effects of their heart condition, or were triggered by surgical trauma – some kids undergo three open-heart surgeries by the time they are one-year-old – a research team led by 马丁·特里斯坦-菲罗齐，m.s.D., is coming to the conclusion that for many of these cases, 遗传学 is the culprit.
"What the field is coming around to is that mutations that cause congenital heart disease sometimes also cause central nervous system disorders. We think it's the combined genetic insult that results in patients having developmental delay,tristan - firouzi说, a pediatric cardiologist and associate professor of pediatrics. The research team is uncovering genetic mutations that affect both the heart and the brain.
Reasoning that most of the straightforward genetic lesions have already been identified – one mutation causing a specific disorder – patient genomes are also undergoing a new type of analysis that measures the cumulative effect of numerous small changes in a patient's DNA, 称为“基因组负荷”. "It examines the overall health of patient genomes," explains co-investigator 马克·杨德尔博士.D., co-director of the USTAR Center for Genetic Discovery and professor of human 遗传学, 谁发明了这项技术. "Certain mutations may hit particularly hard depending on what else is going on in the background."
并行, the researchers are linking detailed accounts of patients' behavioral and developmental challenges to the genetic data. The University Developmental Assessment Center, run by the Department of Pediatrics, examines children with CHDs at strategic developmental periods in their lives: as newborns, 蹒跚学步的, 就在幼儿园之前, 在青春期早期. "Not only does that give us an opportunity to intervene early, but it also allows us to track the kids to see if 遗传学 leads to certain developmental outcomes,” 萨拉·温特，M.D., associate professor of pediatrics and the center's medical director.
Combining clinical information with 基因组学 will eventually allow researchers to construct a road map for precision medicine in CHD patients. "When a child shows up in the clinics, we'd like to be able to predict her long-term outcomes based on genomic sequence, so that treatment can be tailored accordingly,合作研究者说 H. 约瑟夫·约斯特博士.D., Vice Chairman for Basic Science 研究 in Pediatrics and professor of neurobiology and anatomy. As principal investigator on the second grant awarded to the U of U, a renewal of a project initiated in 2009, he is also leading research to discover the biology behind how mutations cause disease, in an effort to develop new treatments.
The two projects join a third U of U clinical effort led by 理查德·威廉姆斯，m.m.D., professor of pediatrics, funded by the NIH program since 2001. 在30多家机构中, the U of U is one of only two to be represented in all three of 从长椅到摇篮's directives: basic science, 基因组学, 以及临床研究.
U of U's strengths stem from investments in multidisciplinary programs, including those designed to push an understanding of the genetic basis of disease. 1.5年前，国家资助 Utah Science Technology and 研究 (USTAR) initiative launched the Center for Genetic Discovery, which has since built a robust pipeline for DNA sequence analysis and innovative tools for deciphering genetic signatures that impact health. In addition, the extensive genealogies combined with medical records represented in the 犹他州人口数据库（UPDB） has proven to be a powerful resource for identifying inherited genetic mutations that cause disease.
What these groups learn from Utah families will be used to help interpret genomic data from 10,在全国范围内治疗了1万名患者, represented within the 从长椅到摇篮 consortium.
"Our highly collaborative team of pediatric clinicians, human geneticists and laboratory scientists at the University of Utah is focused on finding the causes of these devastating diseases that arise before birth and that cause problems throughout life,约斯特说。. "The goal of this nation-wide effort is to develop long-term treatment plans for these children."