Mutations in the myelin protein zero gene associated with Charcot-Marie-Tooth disease type 1B

Abstract

Charcot-Marie-Tooth type 1 (CMT1) disease is an autosomal dominant neuropathy of the peripheral nerve. The majority of CMT 1 cases are due to a duplication of an 1.5-Mb DNA fragment on chromosome 17p11.2 (CMT 1a). Micromutations were found in the gene for peripheral myelin protein 22 (PMP22) located in the duplicated region of CMT 1a, and in the peripheral myelin protein zero (PO) located on chromosome 1q21-q23 (CMT 1b). We have characterized two new mutations in the PO gene in two french families presenting CMT disease. Both mutations occur in the extracellular domain of the PO protein. One mutation is a de novo mutation and is from paternal origin.

Peripheral neuropathies caused by mutations in the myelin protein zero

“…With the advent of genetic testing for mutations, it became apparent that patients diagnosed with both CH [21,22,36,37] and DSD [22,38,39] can have de novo MPZ mutations. Moreover, these neuropathies were often subsequently transmitted in an autosomal dominant fashion [40]. Because these disorders were not recessively inherited, it has become difficult to determine which diagnosis to give certain patients.…”

Autonomic and respiratory dysfunction in Charcot–Marie–Tooth disease due to Thr124Met mutation in the myelin protein zero gene

“…CMT1A is mostly caused by a duplication of the PMP22 gene on chromosome 17p11.2-p12 (Timmerman et al, 1992;Valentijn et al, 1992). CMT1B is associated with mutations in the myelin protein zero (MPZ) gene on chromosome 1q22 -q23 (Hayasaka et al, 1993;Latour et al, 1995). Three clinical and electrophysiological phenotypes have been associated with MPZ gene mutations: CMT1B, which is characterized by slow MNCV (, 25 m/s) and onset in the first two decades of life, Dejerine -Sottas syndrome with onset in infancy and extremely reduced MNCV (, 10 m/s), and congenital hypomyelination (Warner et al, 1996).…”

Mutations of the same sequence of the myelin P0 gene causing two different phenotypes

“…Several mutations in the PO gene have been reported in the literature so far (Rautenstrauss et al, 1994;Latour et al, 1995;Blanquet-Grossard et PO is the most abundant protein of peripheral nervous system myelin, and seems to be essential both for processing of the myelin membrane and for the maintenance of the compact structure of mature myelin (Lemke et al, 1985). The extracellular domain shows similarities with members of the immunoglobulin superfamily and had been hypothesized as taking part in myelin compaction by homophilic interaction.…”