Nature: researchers discover new genetic diseases

February 24, 2020 / BIOON / -- research started from zebrafish has now pointed out the role of collagen secretion in various clinical symptoms, as well as in a newly discovered genetic syndrome Dr ELA knapik, associate professor of medicine at Vanderbilt University Medical Center, and her colleagues discovered the syndrome caused by a single gene mutation and named it catifa, which is the acronym for its core symptoms: cleft palate, cataracts, tooth deformities, intellectual disabilities, facial deformities and ADHD The study, recently published in nature medicine, combines three sources of information: a zebrafish model, a child genetic disease and an electronic health record database related to DNA biobanks Source: ELA knapik, associate professor of cell and developmental biology at M.D Vanderbilt University, said: "these three data sources have their own advantages and disadvantages in disease discovery So I thought, why don't we use them at the same time? "Knapik and her team are working on the function of a gene called ric1 in zebrafish They knew that the mutation in ric1 disrupted collagen production and led to craniofacial and other bone defects in fish They learned that another group of researchers had reported mutations in the ric1 gene in multiple children in a child cataract family Knapik's team evaluated cataracts in zebrafish, but found no cataracts The story may be over, but knapik is interested Do children have other symptoms that are not described because their most pressing problem is cataracts? What are these symptoms? To find more symptoms, knapik and her colleagues at Vanderbilt Institute of genetics turned to biovu, Vanderbilt University's DNA biobank and electronic health record database Dr Eric gamazon, director of the Vanderbilt Institute of genetics and Dr Nancy Cox, Professor of genetics, worked together to develop a computational method (predixcan) to correlate gene regulatory gene expression with the clinical characteristics of patients including in electronic health records When applied to biovu, this method can find a series of clinical features related to the reduction of specific gene expression The list they generated to reduce ric1 expression matches the characteristics observed by knapik and her team in fish, she said "I knew at the time that we needed more information about ric1 mutations and children with cataracts "Saudi Arabia's team reported patients with ric1 mutations and agreed to reassess the list of biovu derived symptoms in these patients Knapik said investigators were surprised to find that their patients developed a series of symptoms: eight children from two related families Knapik said the symptoms of the new disease, catifa, could be explained by a loss of collagen function Collagen is the main structural component of extracellular matrix and the "mortar" between "bricks" Using zebrafish, knapik and her team were able to identify ric1 protein as part of the cellular mechanism that processes and transports collagen out of cells "Without ric1, there would be no collagen transport, no matrix," knapik said "This leads to a wide range of symptoms that we find in the electronic health records of adults and children "Knapik said the findings support the concept of a continuum between rare Mendelian disease, a disease caused by a single gene mutation, and the complex characteristics of common diseases Knapik added that understanding the underlying mechanism and possible symptoms of the disease will improve and personalize care for children with catifa and adults with similar symptoms due to low ric1 activity Knapik said the study provides a new paradigm for accelerating the discovery of disease mechanisms "The knowledge gained from animal models, bioinformatics of human common diseases and rare Mendelian diseases can give us a complete understanding of gene function, so as to move towards better diagnosis, treatment and prevention," she said "Reference: ELA w knapik et al Physio based approach identities ric1 linked Mendelian syndrome through zebrafish models, biobank associations and clinical studies, Nature Medicine (2020) Doi: 10.1038/s41591-019-0705-y