Sousa et al. (Nature genetics, volume 46 (1) 2013: 70-76) recently reported that mutations in PTDSS1 cause Lenz-Majewski Syndrome (LMS). This discovery was made via whole exome sequencing on 4 affected patients. The mutations are gain of function mutations that impair negative feedback regulation of the end product, phosphatidylserine, Interestingly, while synthesis of phosphatidylserine is increased, cellular content does not seem to be altered. This is possibly due to tight regulation of phospholipid content in cells. The mechanism as to how these mutations lead to the clinical features in LMS is not yet known.
Hilary Vernon, MD PhD