The gene for a newly recognized disease has been identified thanks to the determination of an Amish father and the clinical skills and persistence of Indiana University and Riley Hospital for Children physicians in collaboration with physicians and researchers at the Clinic for Special Children in Lancaster County, Penn., which specializes in disorders of the Amish.
The identification of the new multisystem autoimmune disorder and the recessive gene that causes it have been published early online and are reported in the 12 March 2010 print issue of the American Journal of Human Genetics.
The quest began when Jean P. Molleston, M.D., examined a young Amish boy whose family was looking for answers to why the child was not growing well, was developmentally delayed, had chronic diarrhea, and looked different from other children. In spite of numerous medical tests, which confirmed an enlarged liver and spleen, the cause of his multiple medical problems went undefined.
The search gained impetus for Dr. Molleston, an IU School of Medicine professor of pediatrics and Riley Hospital gastroenterologist, when a younger sibling was born with the same characteristics. Shortly thereafter, it also was recognized that a young cousin had similar problems.
Dr. Molleston and her colleagues had three cases and they reached out to Eric Puffenberger, Ph.D., Kevin Straus, M.D., and Holmes Morton, M.D., at the Clinic for Special Children, an innovative clinic dedicated to the unique needs of the Amish which employs cutting edge technology to search for genetic disorders. Blood samples and medical data on the children were sent for analysis. There experts were able to determine that an area of chromosome 20 was abnormally prominent in all three boys but not in unaffected children.
At this time Dr. Molleston and then IU School of Medicine pediatric resident Naomi Lohr, M.D., with the help of the father of the first child, conducted field screening in rural northeastern Indiana to search for additional affected children. Meanwhile, the Lancaster County team learned of a fourth child with similar problems who had multiple autoimmune disorders as had several of the Indiana children. Soon they were aware of a total of ten (7 boys and 3 girls) Amish children, with the oldest in his early twenties, who had the unrecognized multisystem disease. All the children were Indiana Old Order Amish (although some no longer lived in Indiana) and were related.
"It was recognizing autoimmune problems, including autoimmune hepatitis and lung and thyroid problems, that led us to focus our efforts to determine that the responsible gene was one identified as ITCH, one of 250 genes in the region of chromosome 20 identified by the Clinic for Special Children team," said Dr. Molleston.
"We found that all the affected children had a mutation in ITCH, a gene which helps in ubiquination, the chaperoning or transporting of proteins around the cell. Ubiquination tells proteins where to go and what to do and it's particularly important in damping down the immune system so it's not overactive. Ubiquitination has many other important roles in the body's cells, possibly explaining some of the other problems these children have," she elaborated.
"Now that the gene has been identified and we are aware of several autoimmune diseases involved, the heavy lifting of identifying and helping these children can begin. We hear often from the father who brought the first child to us. As we all do, he hopes that now that we have identified the gene, we can quickly find effective treatment. But there are a lot of things going on in this disease and it's going to take much more research to find what's wrong with these children, whether environmental or other as yet unidentified factors contribute, and ultimately to develop drugs to affect ITCH without harming the children," she said.
###
Indiana University School of Medicine: http://www.medicine.iu.edu/ Thanks to Indiana University School of Medicine for this article.
This article has been viewed 134 time(s).
 |
 Digg |
 FarkIt |
 |
 StumbleUpon |
 del.icio.us |
 |
In 1824, three years before he began to publish his famous "double elephant folio" The Birds of America, John James Audubon (1785-1851), the eminent artist of American birds and animals, created a drawing of a running grouse for use in the design for a New Jersey bank note.
The recent discovery of more than a thousand genes known as large intergenic non-coding RNAs (or "lincRNAs") opened up a new approach to understanding the function and organization of the genome. That surprising breakthrough is now made even more compelling with the finding that dozens of these lincRNAs are induced by p53, the most commonly mutated gene in cancer
A genetics research team based at The Children's Hospital of Philadelphia continues to discover recurrent translocations—places in which two chromosomes exchange pieces of themselves. As many as 1 in 600 persons carry balanced chromosome translocations, which involve no loss or gain of DNA.
Some trees growing in nutrient-poor forest soil may get what they need by cultivating specific root microbes to create compounds they require. These microbes are exceptionally efficient at turning inorganic minerals into nutrients that the trees can use. Researchers from France report their findings in the July 2010 issue of the journal Applied and Environmental Microbiology.
"Macho, macho man. I've got to be, a macho man. Macho, macho man. I've got to be a macho!" — The Village People
"If one finds something once, it's accidental. If it is found twice, it's puzzling. If found thrice, there is a pattern," the archaeologists Olle Hemdorff and Eva Thäte say.
"In laboratory tests, right- and left-handers associate positive ideas like honesty and intelligence with their dominant side of space and negative ideas with their non-dominant side," says Daniel Casasanto of the Max Planck Institute for Psycholinguistics in Nijmegen, Netherlands.
Often causing no symptoms in carriers of the disease, worldwide tuberculosis (TB) infects eight to ten million people every year, kills two million, and it is highly contagious as it is spread through coughing and sneezing.