The spleen is rarely noticed, until it is missing. In children born without this organ, that absence is usually not noticed until the children become sick with life-threatening bacterial infections. An international team of researchers led by scientists from Rockefeller University's St. Giles Laboratory of Human Genetics and Infectious Diseases in New York City has now identified the defective gene responsible for this rare disorder. The findings, reported online on April 11, 2013 in Science Express, may lead to new diagnostic tests and raise new questions about the role of this gene in the body's protein-making machinery. Medically known as isolated congenital asplenia (ICA), this condition has only been officially documented in fewer than 100 cases in the medical literature. Alexandre Bolze, a visiting student in the St. Giles lab, headed by Dr. Jean-Laurent Casanova, set out to identify the gene responsible for ICA. He and his colleagues conducted an international search for ICA patients, and identified 38 affected individuals from 23 families in North and South America, Europe, and Africa. Bolze and his team sequenced 23 exomes – all DNA of the genome that codes for proteins – one from each family. After filtering two public databases of genetic information for gene variations in controls, the researchers were left with more than 4,200 possible genes. To narrow this list of candidate genes further, Bolze hypothesized that the disease-causing gene would be more frequently mutated in the ICA exomes compared to control exomes. He then compared the exome sequences of the 23 ICA kindreds with exomes sequenced in the Casanova lab from 508 patients with diseases other than those caused by bacterial infections.
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