EARLY ONSET DEMYELINATING CHARCOT‐MARIE‐TOOTH DISEASE CAUSED BY A NOVEL IN‐FRAME ISOLEUCINE DELETION IN PERIPHERAL MYELIN PROTEIN 2

BACKGROUND AND AIMS: Peripheral Myelin Protein 2 (PMP2) is a small protein located on the cytoplasmic side of compact myelin, involved in the lipids transport and in the myelination process. In the last years few families affected with demyelinating Charcot-Marie-Tooth neuropathy (CMT1), caused by PMP2 mutations, have been identified. In this study we describe the first case of a PMP2 in-frame deletion. METHODS: PMP2 was analyzed by direct sequencing after exclusion of the most frequent CMT-associated genes by using a Next Generation Sequencing (NGS) genes panel. Sanger sequencing was used for family's segregation analysis. Molecular modelling analysis was used to evaluate the mutation impact on the protein structure. RESULTS: A novel PMP2: p.I50del has been identified in a child with early onset CMT1 and in three affected family members. All family members show an early onset demyelinating neuropathy without other distinguish features. Molecular modelling analysis and in silico evaluations do not suggest a strong impact on the overall protein structure, but a most likely altered protein function. INTERPRETATIONS: This study suggests the importance to add PMP2 in CMT NGS genes panels or, at most, to test it after major CMT1 genes exclusion, due to the lack of diagnostic-addressing additional features. This article is protected by copyright. All rights reserved.