Perlman syndrome gene identified

Pruijn, Ger

In a recent collaboration of scientists from the UK, Italy, USA and the Netherlands scientists have uncovered mutations in a gene, DIS3L2, leading to increased susceptibility to Perlman syndrome. The findings have been published in a top scientific journal, Nature Genetics.

DIS3L2 is known to encode a member of a family of exonucleases, enzymes that degrade RNA molecules. The authors demonstrated that in patients with Perlman syndrome the DIS3L2 exonuclease is inactive. The exact consequences of this are still unknown but ultimately this leads to abnormal embryo development and increased risk of Wilms tumours.

Perlman syndrome is a rare autosomal recessive overgrowth disorder present at birth (estimated incidence 1:1,000,000). Patients have abnormally large organs, abnormal facial features and kidney dysfunction. Most patients die within the first months of life.

Which RNA molecules are specifically targeted by DIS3L2 and how expression of DIS3L2 protein could be returned to normal will provide vital clues for the discovery of therapy.

Dewi Astuti, Mark R Morris, Wendy N Cooper, Raymond H J Staals, Naomi Wake, Graham A Fews, Harmeet Gill, Dean Gentle, Salwati Shuib, Christopher J Ricketts, Trevor Cole, Anthonie J van Essen, Richard van Lingen, Giovanni Neri, John M Opitz, Patrick Rump, Irene Stolte-Dijkstra, Ferenc Müller, Ger J M Pruijn, Farida Latif & Eamonn R Maher. Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. Nature genetics, 5th January 2012.


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