Neuropathy target esterase impairments cause Oliver-McFarlane and Laurence-Moon syndromes

Here, we identified recessive mutations in the PNPLA6 gene, encoding Neuropathy Target Esterase (NTE) protein, responsible for Oliver-McFarlane and Laurence-Moon syndromes in humans. Our finding expands the spectrum of PNPLA6-associated diseases to include hair abnormalities and pituitary atrophy, which can lead to intellectual disability and short stature. We further link the mechanisms among other PNPLA6-associated diseases, including Spastic Paraplegia Type 39, by surveying normal human embryonic expression in eye, pituitary and brain, and by analyzing the effects of PNPLA6 mutations on NTE function both in zebrafish and patient cells. Our results suggest that the common cause of these disorders is NTE loss-of-function, and that the extent of remaining NTE function may help define the course of disease. (By Drs. Robert Hufnagel and Zubair M. Ahmed, http://jmg.bmj.com/content/early/2014/12/05/jmedgenet-2014-102856 )