PNPLA6-related disorders have been implicated in a broad spectrum of neurodegenerative disorders. The phenotypic spectrum includes at least four clinical key features: ataxia, motor neuron disease (upper motor neuron disease with or without additional lower motor neuropathy), hypogonadism, and chorioretinal dystrophy. Although these clinical features appear to be frequent in PNPLA6 disease none of them is an obligate feature of the disease. The majority of the PNPLA6 mutations affect a phospholipid esterase domain in neuropathy target esterase (NTE), which has been shown to de-esterify phosphatidylcholine, a major component of biological membranes, into its constituent fatty acids and glycerophosphocholine. Other phenotypes caused by NTE dysfunction due to PNPLA6 mutations include anterior hypopituitarism, trichomegaly, alopecia, and facial dysmorphisms.
Synofzik M, Gonzalez MA, Lourenco CM, Coutelier M, Haack TB, Rebelo A, Hannequin D, Strom TM, Prokisch H, Kernstock C, Durr A, Schols L, Lima-Martinez MM, Farooq A, Schule R, Stevanin G, Marques W Jr, Zuchner S
Title
PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum.
