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A missense mutation in human INSC causes peripheral neuropathy

ABSTRACT: PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209T>G (p.Met70Arg) in the INSC gene. Modelling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlights a potential therapeutic target for INSC-associated CMT2.

SUBMITTER: Jui-Yu Yeh

PROVIDER: S-SCDT-10_1038-S44321-024-00062-W | biostudies-other |

REPOSITORIES: biostudies-other

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A Novel Missense Mutation in Peripheral Myelin Protein-22 Causes Charcot-Marie-Tooth Disease.

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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