X‐linked Charcot–Marie–Tooth disease predominates in a cohort of multiethnic Malaysian patients

Shahrizaila, Nortina; Samulong, Sarimah; Tey, Shelisa; Suan, Liaw Chiew; Meng, Lao Kah; Goh, Khean Jin; Ahmad‐Annuar, Azlina

doi:10.1002/mus.23892

Cited by 9 publications

(13 citation statements)

References 24 publications

(39 reference statements)

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“…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). 6,8,20,[27][28][29][30][31][32][33] In our study, 65 patients were identified with CMT1.…”

Section: Discussionmentioning

confidence: 78%

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

et al. 2019

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Charcot‐Marie‐Tooth (CMT) disease is a heterogeneous group of inherited sensorimotor neuropathies. To clarify the genetic spectrum and clinical profiles in Chinese CMT patients, we enrolled 150 unrelated CMT patients from southeast China. We performed multiplex ligation‐dependent probe amplification (MLPA) testing in all patients and next‐generation sequencing (NGS) among those patients without PMP22 rearrangements. We identified PMP22 duplications in 40 patients and deletions in 12 patients. In addition, we found 19 novel variants and 36 known mutations in 57 patients. Among these 55 variants, 45 pathogenic or likely pathogenic variants were identified in 48 cases, and 10 variants with uncertain significance were identified in 9 cases. Therefore, we obtained a genetic diagnosis in 63.8% (88/138) of CMT patients and 66.7% (100/150) of all included patients. PMP22, GJB1, and MFN2 are the most common causative genes in CMT1 (demyelinated form), intermediate CMT, and CMT2 (axonal form), respectively. In this study, we identified a higher proportion of intermediate CMT, a relatively high frequency of NDRG1 mutations and clinical features of later onset age in CMT1A patients. Our results broaden the genetic and clinical spectrum of CMT patients, which can help optimize the genetic and clinical diagnosis.

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Section: Discussionmentioning

confidence: 78%

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

et al. 2019

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“…24 The mutation frequency in MPZ analogous to those Chinese patient patient's cohort and some Asian groups (Korea and Malaysia), but was lower than that of the Japanese (Table 4). 5,12,[15][16][17][18][19][20][21][22][23][24][25][26][27] For the other patients, the disease-causing mutations were detected by targeted NGS. In our study, we designed a phenotypespecific panel, included 85 genes related to CMT and other inherited peripheral neuropathies, which apply to detect inherited peripheral neuropathies including CMT, distal hereditary motor neuronopathy (dHMN), hereditary sensory and autonomic neuropathy (HSAN) and hereditary neuralgic amyotrophy (HNA) ( Table S1).…”

Section: Discussionmentioning

confidence: 99%

“…4,33,34 The clinical feature, EMG examination and sural nerve biopsy reminded us that the patient was diagnosed with demyelinating CMT ( Figure 5 and Table 3 (Table 4). 5,12,[15][16][17][18][19][20][21][22][23][24][25][26][27] In conclusion, the results of this study will help to optimize the genetic diagnosis algorithm in Chinese demyelinating CMT patients.…”

Section: Discussionmentioning

confidence: 99%

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

Guo

et al. 2018

J Peripheral Nervous Sys

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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.

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“…[24] In a study of multi-ethnic Malaysian patients with CMTs ( n = 25), CMT1X patients were all Chinese and accounted for 24% of the total CMT patients. [25]…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in the EC1 and EC2 domains of Cx32 were in 65% of the patients with Spanish or Portuguese descent. [41] However, EC1 and EC2 were not hotspot mutation domains in Japanese[24] and Malaysian[25] patients. We found no relationship between the position of mutations and CNS involvement in CMT1X.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Features of Chinese X-linked Charcot-Marie-Tooth Type 1 Disease

Lyu

Jin

et al. 2017

Chinese Medical Journal

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Background:X-linked Charcot-Marie-Tooth type 1 (CMT1X) disease is one of the most common forms of inherited neuropathy caused by mutations in the gap junction beta-1 protein (GJB1) gene (also known as connexin 32). This study presented the clinical and genetic features of a series of Chinese patients with GJB1 gene mutations.Methods:A total of 22 patients from unrelated families, who were referred to Department of Neurology, Peking University First Hospital from January 2005 to January 2016, were identified with GJB1 mutations. Their clinical records and laboratory findings were retrospectively collected and reviewed. Mutations in the GJB1 gene were analyzed by targeted next-generation sequencing (NGS). Nucleotide alternations were confirmed with Sanger sequencing.Results:The CMT1X patients predominantly showed distal muscle weakness of lower limbs with mild sensory disturbance. The mean age of onset was 15.6 ± 8.7 years (ranging from 1 year to 42 years). The sudden onset of cerebral symptoms appeared in four patients (18.2%); two were initial symptoms. One case had constant central nervous system (CNS) signs. There were 19 different heterozygous mutations, including 15 known mutations and four novel mutations (c.115G>T, c.380T>A, c.263C>A, and c.818_819insGGGCT). Among the 22 Chinese patients with CMT1X, the frequency of the GJB1 mutation was 4.5% in transmembrane domain 1 (TM1), 4.5% in TM2, 22.7% in TM3, 9.1% in TM4, 4.5% in extracellular 1 (EC1), 27.3% in EC2, 9.1% in intracellular loop, 13.6% in the N-terminal domain, and 4.5% in the C-terminal domain. CMT1X with CNS impairment appeared in five (22.7%) of these patients.Conclusions:This study indicated that CNS impairment was not rare in Chinese CMT1X patients. Mutations in the EC2 domain of the GJB1 gene were hotspot in Chinese CMT1X patients.

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X‐linked Charcot–Marie–Tooth disease predominates in a cohort of multiethnic Malaysian patients

Abstract: X-linked Charcot-Marie-Tooth disease was found to predominate in our patient cohort. We also found a better phenotype/genotype correlation when applying a more recently recommended genetic approach to Charcot-Marie-Tooth disease.

Cited by 9 publications

References 24 publications

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

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

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

Clinical and Genetic Features of Chinese X-linked Charcot-Marie-Tooth Type 1 Disease

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