%0 Journal Article
%T Two novel missense mutations in the myelin protein zero gene causes Charcot-Marie-Tooth type 2 and D¨¦j¨¦rine-Sottas syndrome
%A Geir J Braathen
%A Jette C Sand
%A Michael B Russell
%J BMC Research Notes
%D 2010
%I BioMed Central
%R 10.1186/1756-0500-3-99
%X One novel missense mutation caused a milder late onset CMT type 2, while the second missense mutation caused a severe early onset phenotype compatible with D¨¦j¨¦rine-Sottas syndrome.The phenotypic variation caused by different missense mutations in the MPZ gene is likely caused by different conformational changes of the MPZ protein which affects the functional tetramers. Severe changes of the MPZ protein cause dysfunctional tetramers and predominantly uncompacted myelin, i.e. the severe phenotypes congenital hypomyelinating neuropathy and D¨¦j¨¦rine-Sottas syndrome, while milder changes cause the phenotypes CMT type 1 and 2.Charcot-Marie-Tooth (CMT) disease is characterized by distal muscle wasting and weakness, sensory loss with reduced tendon reflexes and foot deformities [1,2]. It is the most common inherited disorder of the peripheral nervous system with an estimated prevalence of 1 in 2,500 [3]. CMT is a heterogeneous disorder with respect to clinical features, neurophysiology, pathophysiology and genetics. The number of identified CMT genes is still expanding. So far the majority of the CMT genes encodes either neuronal or Schwann cell proteins [4]. However, the most frequent autosomal recessive form of CMT is caused by mutation in the glioside-induced differentiation-associated protein-1 (GDAP1) gene, which is located in the mitochondrial outer membrane and expressed in both neurons and Schwann cells [5].The myelin protein zero (MPZ) gene encodes a leader peptide of 29 amino acids which is cleaved from the remaining 219 amino acids before insertion in the myelin sheath [6]. The myelin protein zero (P0) is post-translationally modified by additions of multiple sulphate, acyl and phosphate groups and an N-linked oligosaccharide [7,8]. P0 has an extracellular, a transmembrane and a cytoplasmic domain. It is the most abundant protein in the myelin sheath of the peripheral nervous system [9]. The extracellular domain from myelin protein zero protein (P0ex) mediates h
%U http://www.biomedcentral.com/1756-0500/3/99