Clinical and genetic investigation in Chinese patients with demyelinating Charcot‐Marie‐Tooth disease

Abstract

Demyelinating Charcot-Marie-Tooth disease (CMT) is the most common subtype of CMT. It is caused mainly by 17p11.2 heterozygous duplication, but also by mutations in more than 20 genes which affect development and function of Schwann cells. To investigate the profile of genes mutated and clinical features in demyelinating CMT of Chinese descent, we collected a cohort of 44 demyelinating CMT patients and screened them using multiplex ligation-dependent probe amplification (MLPA) and targeted next-generation sequencing (NGS) technology. The MLPA technology revealed that 77.3% demyelinating CMT patients harbored 17p11.2 heterozygous duplication and 6.8% patients harbored heterozygous deletion of exon 6 of MPZ gene, that was further confirmed a novel c.674_675insA mutation in MPZ gene. In the patients with 17p12 heterozygous duplication, 3 sets of independent families were discordant for the CMT phenotype within the same family. The targeted NGS technology revealed that 6 candidate mutations including 1 previously reported mutation (GDAP1: c.571C>T) and 5 novel mutations (SBF2: c.415T>C, c.619G>T, c.1258A>G; GDAP1: c.589delC; PMP22: c.318delT) were found. In conclusion, combined MLPA technique with targeted NGS, the demyelinating CMT genetic diagnostic success rate was increased.

Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot‐Marie‐Tooth disease

“…However, the genetic spectrum we report in our CMT patient series partly differs from the results of previous studies of Chinese CMT patients. The PMP22 duplication was detected in 62.5% CMT1 patients in the study by Song et al but was much lower (31.0%) in the study by Wang et al Another study conducted by He et al showed a high frequency (77.3%) of PMP22 duplications in CMT1 patients . The study conducted by Sun et al suggested PMP22 duplication accounted for 50% of CMT1 cases .…”

“…The PMP22 duplication was detected in 62.5% CMT1 patients in the study by Song et al 21 but was much lower (31.0%) in the study by Wang et al 22 Another study conducted by He et al showed a high frequency (77.3%) of PMP22 duplications in CMT1 patients. 23 The study conducted by Sun et al suggested PMP22 duplication accounted for 50% of CMT1 cases. 19 In studies conducted in other Asian CMT patients, the frequencies of PMP22 duplication ranged from 23.3% to 53.6% of CMT1, [24][25][26] which was generally lower than those reported in European and American studies (53.7-76.3% of CMT1 patients).…”

Identification and functional characterization of novel GDAP1 variants in Chinese patients with Charcot-Marie-Tooth disease

“…It is noticeable, however, all the patients with GDAP1 variants in our study presented axonal type of neuropathy which was consist with previous studies in Chinese patients except one of patients reported by He J (He et al, 2018). Actually, this case showed an absent MNCV and CMAPs in median nerve as no response by electrophysiological detection that caused difficulty in defining its clinical type.…”

ATP1A1mutations cause intermediate Charcot‐Marie‐Tooth disease

“…All patients corresponded with the intermediate CMT diagnostic standard (25 m/s < MNCV < 45 m/s; Berciano et al, ; Liu & Zhang, ). By using the CMT related gene panel which was described in the previous study, the common pathogenic genes were screened in these patients (He et al, ). Of the remaining molecularly unassigned intermediate CMT families, we have identified two heterozygous mutations in ATP1A1 gene (NM_000701.8), in two intermediate CMT pedigrees respectively, including six patients and 10 unaffected individuals.…”