Severe Consequences of SAC3/FIG4 Phosphatase Deficiency to Phosphoinositides in Patients with Charcot-Marie-Tooth Disease Type-4J.

ABSTRACT: Charcot-Marie-Tooth disease type-4J (CMT4J), an autosomal recessively inherited peripheral neuropathy characterized by neuronal degeneration, segmental demyelination, and limb muscle weakness, is caused by compound heterozygous mutations in the SAC3/FIG4 gene, resulting in SAC3/FIG4 protein deficiency. SAC3/FIG4 is a phosphatase that not only turns over PtdIns(3,5)P₂ to PtdIns3P but also promotes PtdIns(3,5)P₂ synthesis by activating the PIKFYVE kinase that also makes PtdIns5P. Whether CMT4J patients have alterations in PtdIns(3,5)P₂, PtdIns5P or in other phosphoinositides (PIs), and if yes, in what direction these changes might be, has never been examined. We performed PI profiling in primary fibroblasts from a cohort of CMT4J patients. Subsequent to myo-[

SUBMITTER: Shisheva A 

PROVIDER: S-EPMC11995980 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature