Schwann cell transcript biomarkers for hereditary neuropathy skin biopsies

Charcot-Marie-Tooth (CMT) disease is most commonly caused by duplication of a chromosomal segment surrounding Peripheral Myelin Protein 22, or the PMP22 gene, which is classified as CMT1A. Several candidate therapies reduce Pmp22 mRNA levels in CMT1A rodent models, but the development of biomarkers for clinical trials in CMT1A is a challenge, given its slow progression and difficulty in obtaining nerve samples. Quantitative PCR measurements of PMP22 mRNA in dermal nerves were performed using skin biopsies in human clinical trials for CMT1A, but this approach did not show increased PMP22 mRNA in CMT1A patients compared to controls. One complicating factor is the variable amounts of Schwann cells (SCs) in the skin. The objective of the study was to develop a novel method for precise evaluation of PMP22 levels in skin biopsies that can discriminate CMT1A patients from controls. We have developed methods to normalize PMP22 transcript levels to SC-specific genes that are not altered by CMT1A..., Two 2-mm punch skin biopsies were performed 9cm proximal to the ulnar crease and placed in RNAlater (Thermo Fisher Scientific, Waltham, MA) before freezing, as previously described 12, 13, 24-26. Total RNA isolated from the samples was prepared for RNA-seq using NuGEN Ovation library prep kits.
Nanostring Analysis. The custom 54-gene Codeset was designed by Nanostring to maximize detection of most transcript variants, except the probes targeted to exons 1A and 1B of the PMP22 gene. SC-specific expression was also assessed using profiling of sorted cell types in mouse embryonic skin.30 Total RNA was extracted from skin biopsies by homogenization/purification with the TRIzol reagent and then further purified using the Qiagen RNeasy MinElute Cleanup Kit (catalog no.: 74204; Qiagen, Hilden, Germany). Samples were assessed for concentration, purity, and quality by NanoDrop and Bioanalyzer (Agilent RNA6000 PicoChip; Agilent Technologies, Santa Clara, CA). The nCounter..., , # Skin transcript biomarkers for Charcot-Marie-Tooth Disease

[https://doi.org/10.5061/dryad.hqbzkh1st](https://doi.org/10.5061/dryad.hqbzkh1st)

## Description of the data and file structure

Nanostring panel data for skin biopsies from control and CMT1A

The spreadsheet (2019_nanostring_paper_samples_(jpsvaren_wisc.edu).xlsx) contains raw data from the custom Nanostring panel assays of control and CMT1A skin biopsies: Schwann cell transcript biomarkers for hereditary neuropathy skin biopsies Annals Neurology. 2019 Jun;85(6):887-898. doi: 10.1002/ana.25480. Epub 2019 Apr 22. PMID: 30945774 PMCID: PMC7050273 (also available as free PMC article [https://pmc.ncbi.nlm.nih.gov/articles/PMC7050273/](https://pmc.ncbi.nlm.nih.gov/articles/PMC7050273/))

The first tab has design data for the targeted human transcripts, including the target sequence and predicted melting temperature. 2nd tab has the pilot data from Figure 2 (21 CMT1A, 4 control), which includes raw count data generated from the ...,