The PMP22 Gene and Its Related Diseases

• Published in: Molecular neurobiology 2013-04, Vol.47 (2), p.673-698
• Main Authors: Li, Jun, Parker, Brett, Martyn, Colin, Natarajan, Chandramohan, Guo, Jiasong
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Charcot-Marie-Tooth disease; Charcot-Marie-Tooth Disease - genetics; Charcot-Marie-Tooth Disease - metabolism; Charcot-Marie-Tooth Disease - pathology; Glycoproteins; Humans; Molecular Sequence Data; Mutation; Mutation - genetics; Myelin Proteins - genetics; Myelin Proteins - physiology; Nervous system; Neurobiology; Neurology; Neurosciences; Peripheral Nervous System Diseases - genetics; Peripheral Nervous System Diseases - metabolism; Peripheral Nervous System Diseases - pathology; Proteins; Spinal cord
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-012-8370-x

Peripheral myelin protein-22 (PMP22) is primarily expressed in the compact myelin of the peripheral nervous system. Levels of PMP22 have to be tightly regulated since alterations of PMP22 levels by mutations of the PMP22 gene are responsible for >50 % of all patients with inherited peripheral neuropathies, including Charcot–Marie–Tooth type-1A (CMT1A) with trisomy of PMP22 , hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of PMP22 , and CMT1E with point mutations of PMP22 . While overexpression and point-mutations of the PMP22 gene may produce gain-of-function phenotypes, deletion of PMP22 results in a loss-of-function phenotype that reveals the normal physiological functions of the PMP22 protein. In this article, we will review the basic genetics, biochemistry and molecular structure of PMP22, followed by discussion of the current understanding of pathogenic mechanisms involving in the inherited neuropathies with mutations in PMP22 gene.