A Rare Myelin Protein Zero

• Published in: PloS one Vol. 5; no. 12; p. e14346
• Main Authors: Antonellis, Anthony, Dennis, Megan Y, Burzynski, Grzegorz, Huynh, Jimmy, Maduro, Valerie, Hodonsky, Chani J, Khajavi, Mehrdad, Szigeti, Kinga, Mukkamala, Sandeep, Bessling, Seneca L, Pavan, William J, McCallion, Andrew S, Lupski, James R, Green, Eric D
• Format: Journal Article
• Language: English
• Published: Public Library of Science 16.12.2010
• Subjects: Analysis; DNA binding proteins; Genes; Genetic aspects; Nervous system diseases; Protein binding; Transcription (Genetics)
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0014346

Myelin protein zero (MPZ) is a critical structural component of myelin in the peripheral nervous system. The MPZ gene is regulated, in part, by the transcription factors SOX10 and EGR2. Mutations in MPZ, SOX10, and EGR2 have been implicated in demyelinating peripheral neuropathies, suggesting that components of this transcriptional network are candidates for harboring disease-causing mutations (or otherwise functional variants) that affect MPZ expression. We utilized a combination of multi-species sequence comparisons, transcription factor-binding site predictions, targeted human DNA re-sequencing, and in vitro and in vivo enhancer assays to study human non-coding MPZ variants. This is the first reported MPZ variant within a cis-acting transcriptional regulatory element. While we were unable to implicate this variant in disease onset, our data suggests that similar non-coding sequences should be screened for mutations in patients with neurological disease. Furthermore, our multi-faceted approach for examining the functional significance of non-coding variants can be readily generalized to study other loci important for myelin structure and function.