Two Novel Myelin Protein Zero Mutations in a Group of Chinese Patients

Abstract

Mutations in the myelin protein zero gene are responsible for the autosomal dominant Charcot-Marie-Tooth disease (CMT). We summarized the genetic and clinical features of six unrelated Chinese families and the genetic spectrum of Chinese patients with myelin protein zero (MPZ) mutations. Our study reports data from a group of Chinese patients consisting of five males and one female with the age of disease onset ranging from 16 to 55 years. The initial symptom in all the patients was the weakness of the lower limbs. Electrophysiological presentations suggested chronic progressive sensorimotor demyelinating polyneuropathy. Overall six mutations were identified in the cohort, including four known mutations [c.103G>T (p.D35Y), c.233C>T (p.S78L), c.293G>A (p.R98H), and c.449-1G>T], and two novel mutations [c.67+4A>G with a mild CMT1B phenotype, and (c.79delG) p.A27fs with a rapidly progressive CMT1B phenotype]. According to the literature review, there are 35 Chinese families with 28 different MPZ mutations. The MPZ mutational spectrum in Chinese patients is very heterogeneous and differs from that of Japanese and Korean individuals, although they do share several common hot spot mutations.

Genotype–phenotype characteristics and baseline natural history of Chinese myelin protein zero gene related neuropathy patients

“…However, some scholars have suggested that adult‐onset neuropathy does not necessarily imply that the disease will be mild [27,41]. In our study, although the average CMTNS of adult‐onset patients was lower than that of infantile‐onset patients, no statistically significant difference was observed, possibly because the sample size was insufficient; the infantile patients had a younger age at onset and relatively slower progression, whilst adult patients had an older age at onset and rapid progression [11,42]. The percentage of hearing loss in our study (5.4%) was lower than that reported by Sanmaneechai et al (20.4%) in the USA and was similar to that reported by Taniguchi et al in Japan, indicating that the occurrence of hearing loss might be less frequent in east Asia [24,29].…”

Clinical Features of a Newly Described Mutation of Myelin Protein Zero in a Family

“…More than 300 MPZ gene mutations have been identified as the cause of inherited peripheral neuropathy, exhibiting a wide range of phenotypes with varying severity of clinical symptoms [ 7 , 9 , 13 ]. The early-onset infantile and childhood phenotypes developmentally impair myelination, while the adult-onset phenotypes are characterized by axonal degeneration without prior demyelination [ 7 , 14 ]. Sanmaneechai and colleagues provided detailed descriptions of phenotypes of MPZ mutations from a cohort of 103 patients from 71 families with 47 different mutations [ 15 ].…”

“…Genetic studies confirmed a heterozygous identical variant of MPZ in Exon 2.c109G>A (p.Glu37Lys) for both patients 1 and 2. Inherited in an autosomal dominant fashion, this single-nucleotide variant has a cytogenetic location on chromosome 1q23.3 [ 7 , 12 ]. The variant was deemed to be of uncertain clinical significance by the lab as it has not been reported before.…”

“…While the PMP22 gene mutation is most frequently confirmed in CMT disease, greater than 100 gene mutations are known to cause CMT phenotypes which may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner [ 1 , 7 ]. A type I transmembrane protein consisting of 248 amino acids and a member of the immunoglobulin supergene family, myelin protein zero (MPZ), is the most abundant structural protein in the peripheral nervous system myelin [ 8 , 9 ].…”

“…MPZ gene mutations are being increasingly recognized as causes of certain forms of hereditary peripheral neuropathy including CMT disease and early-onset Dejerine-Sottas disease [ 9 , 10 ]. Affecting 4.1-5% of all CMT patients, MPZ mutations are associated with the autosomal dominant demyelinating neuropathy CMT1B and axonal neuropathy CMT2I/J [ 7 , 9 ]. Additionally, point mutations in the MPZ gene account for 10-12% of all dominant demyelinating CMT type 1 cases [ 10 ].…”