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22-04-2013 | Genetics | Article

Gene responsible for half asplenia cases discovered


Free abstract

medwireNews: Researchers have discovered that mutations in the ribosomal protein SA gene (RPSA) are responsible for around half of all cases of isolated congenital asplenia (ICA).

Alexandre Bolze (Rockefeller University, New York, USA) and colleagues investigated genetic causes behind the condition, characterised by a lack of spleen at birth, in 38 individuals with the condition from 23 families.

As reported in Science, the researchers analysed exome sequence from the individuals with asplenia and compared them with exomes from control participants without the condition. The researchers found that 18 people from eight families had heterozygous mutations in RPSA, corresponding to half the individuals in the cohort and one third of the families.

The RPSA variants included a nonsense mutation and frameshift duplication, as well as five missense mutations. The team found that the mutations result in haploinsufficiency of RPSA and cause autosomal dominant ICA.

"These results are very clear, as at least 50 percent of the patients carry a mutation in RPSA," said Bolze in a press statement. "Moreover, every individual carrying a coding mutation in this gene lacks a spleen."

The researchers say that it is surprising that mutations in a gene such as RPSA can result in a specific physiological alteration such as that seen in individuals with asplenia, as the gene is expressed throughout the body and has not previously been linked to spleen development.

"These results raise many questions. They open up many research paths to understand the specific role of this protein and of the ribosome in the development of organs in humans," said Bolze.

The researchers explain that they still don't fully understand the causes of ICA, but say that "the emerging idea that ribosomes can be "specialized" might account for the narrow phenotype caused by mutations in RPSA.

"Alternatively, an extra-ribosomal function of RPSA may ex-plain the phenotype. The surprising connection between RPSA and spleen development in humans calls for explorations of the underlying mechanisms."

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Helen Albert

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