Gene mutation behind missing spleen in newborns identified

Scientists have identified the defective gene responsible for a rare disorder in which children are born without a spleen, which makes them susceptible to life-threatening bacterial infections.
The findings by an international team of researchers led by scientists from Rockefeller's St Giles Laboratory of Human Genetics and Infectious Diseases in US 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 less than 100 cases in the medical literature.
In humans, the spleen is brownish in colour and is located in the left upper quadrant of the abdomen. It acts primarily as a blood filter. Thus, life is possible after the spleen is removed.

Alexandre Bolze, a visiting student in the St Giles lab, headed by 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 is coding 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 hypothesised 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.
After applying statistical algorithms, Bolze found one gene with high significance: RPSA, which normally codes for a protein found in the cell's protein-synthesising ribosome, according to the findings reported in Science Express.
"These results are very clear, as at least 50 per cent of the patients carry a mutation in RPSA. Moreover, every individual carrying a coding mutation in this gene lacks a spleen," Bolze said.
The findings, Bolze said, are surprising because the ribosome is present in every organ of the body, not just the spleen.