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MPZ Gene (mpz + gene)
Selected AbstractsMyelin thickenings in val 102/fs null mutation of MPZ geneJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004MV De Angelis Myelin thickenings, abnormal myelin foldings and tomacula have been rarely described in CMT1B. In two unrelated patients of different age (patient 1: 29 years old; patient 2: 65 years old) with CMT1B and Val 102/fs null mutation of MPZ gene we performed morphometric analysis, teased fibers and ultrastructural examination of sural nerve. We found: 1) markedly decreased fiber density with prevalent loss of large diameter fibers (patient 1: 4419 fibers/mm2; patient 2: 1326 fibers/mm2); 2) evidence of de-remyelination; and 3) paranodal and internodal myelin thickenings in virtually all fibers. Patient 1 has myelin thickenings measuring more than 50% of the fiber diameter in 14% of fibers and thickenings greater than 30% in 33% of fibers. Patients 2 presents myelin thickenings measuring more than 50% of fiber diameter in 23% of fibers and thickening greater than 30% in 49% of fibers. When considering the absolute measure of myelin thickenings and their number over 100 internodes, patient 1 presents 150 small myelin thickenings (<8 mm of diameter) whereas patient 2 has 57. The number of globules (8,12 mm of diameter) is 56 in patient 1 and 45 in patient 2. The number of myelin thickenings greater than 12 mm is 33 in patient 1 and 45 in patient 2. Ultrathin sections showed myelin infoldings, outfoldings and uncompacted myelin. CMT1B with a heterozygous null mutation of MPZ gene is characterized by abundant focal myelin thickenings. Similar findings have been described in the P0 deficient heterozygous mice. [source] Novel MPZ Mutation In A Sporadic CMT PatientJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001E Bellone Mutations in the gene for the major structural protein component of peripheral nerve myelin, myelin protein zero (MPZ), are associated with some forms of hereditary neuropathies such as Charcot-Marie-Tooth disease type 1B (CMT1B), Dejerine-Sottas syndrome (DSS) and congenital hypomyelinating neuropathy (CHN). The common pathological characteristics of these allelic disorders are severe demyelination and remyelination of peripheral nerves. Recently, MPZ mutations were also found in patients with the axonal form of CMT neuropathy (CMT2). We studied a patient with negative familiar history and clinical and electrophysiological features of Charcot-Marie-Tooth disease: distal muscle weakness and atrophy, foot deformities (pes cavus), and severely reduced nerve conduction velocities in the motor and sensory nerves. The sural nerve biopsy showed marked loss of myelinated fibers, few onion bulbs, and a high percentage of fibers showing excessive myelin outfoldings. DNA analysis excluded CMT1A duplication by Southern blot and by pulsed field gel electrophoresis methods. SSCP analysis of all six exons of MPZ revealed a shift band in exon 2 in the patient's DNA. No such difference was detected in normal controls. Direct sequencing disclosed a G , A transition at nucleotide position 181. This base substitution predicts the replacement of aspartic acid with asparagine at codon 61. A mutation at the same codon (but different amino acid replacement) was recently identified in a family with the axonal type of CMT, in which the disease was autosomal dominantly inherited. This finding provides further confirmation of the role of MPZ gene in peripheral neuropathies and suggests that MPZ coding region mutations may account for a considerable number of CMT cases which do not involve DNA duplication on 17p11.2-p12. This research was partially supported by a MURST and an Ateneo grant to FA, by a Ministero della Sanità grant to PM. Our laboratory is a member of the European Charcot-Marie-Tooth Consortium co-ordinated by Prof. Christine Van Broeckhoven. [source] New mutation of the MPZ gene in a family with the Dejerine,Sottas disease phenotypeMUSCLE AND NERVE, Issue 5 2007Paraskewi Floroskufi MSc Abstract Charcot,Marie,Tooth disease type 1B is associated with mutations in the myelin protein zero gene. In the present study a new myelin protein zero gene mutation (c.89T>C,Ile30Thr) was detected in a family with the Dejerine,Sottas disease phenotype. The results support the hypothesis that severe, early-onset neuropathy may be related to either an alteration of a conserved amino acid or a disruption of the tertiary structure of myelin protein zero. Muscle Nerve, 2006 [source] Axonal and demyelinating forms of the MPZ Thr124Met mutationACTA NEUROLOGICA SCANDINAVICA, Issue 3 2003S. Kurihara Objective , We report on a Japanese family with Charcot,Marie,Tooth disease (CMT) with the Thr124Met mutation in the peripheral myelin protein zero (MPZ) gene. Material and methods , Based on the clinical study, we investigated MPZ gene by direct sequence analysis and polymerase chain reaction,restriction fragment length polymorphism analysis. Results , Genotyping of four symptomatic family members showed that one family member with severe disease symptoms was homozygous, while the other three were heterozygous. The heterozygous cases were clinicopathologically determined to be the axonal type, which is characterized by late-onset and slow progression associated with Adie's pupil and deafness. The homozygous case was the demyelinating type, which showed earlier onset, rapid progression, sural nerve demyelination, and cranial nerve demyelination at autopsy. Conclusions , We suggest that axonal and demyelinating forms of CMT are not two distinct classes, but rather parts of a spectrum of genotypically related conditions, particularly with some MPZ mutations. [source] | ||||||||||