Protein glycosylation: a factor in the pathology of PLAN?

Monday, September 22, 2014 — Poster Session II
4:00 p.m. – 6:00 p.m.	FAES Academic Center	NHGRI	MOLBIO-2

Authors

• M Davids
• MS Kane
• M He
• CF Boerkoel
• WA Gahl
• C Torro

Abstract

Mutations in PLA2G6, encoding the calcium-independent phospholipase A2 group VI have been associated with several forms of neurodegenerative disorders that are described as PLA2G6 associated neurodegeneration (PLAN). Here we describe three patients with different PLAN phenotypes, two presented with infantile neuroaxonal dystrophy (INAD) and one with dystonia-parkinsonism. In all three patients biallelic mutations in PLA2G6 (NM_003560.2) were found; c.[950G>T];[426-1077dup] and, c.[1799G>A];[2222G>T] in the patients with INAD, and c.[609G>A];[2222G>A] in the patient with dystonia-parkinsonism. Upon investigation of the pathogenic mechanism of mutations in PLA2G6, changes of Golgi morphology were noted in cultured fibroblasts and subsequent abnormalities in N-linked and O-linked glycosylation, and sialylation. After rescue by reintroduction of the wild type PLA2G6, Golgi morphology glycosylation, and sialylation normalized. These observations are discussed in the context of their implications for the pathophysiology of PLAN.

back to top