Genetic profile and onset features of 1005 patients with Charcot-Marie-Tooth disease in Japan

Yoshimura, Akinobu; Yuan, Jun‐Hui; Hashiguchi, Akihiro; Ando, Masahiro; Higuchi, Yujiro; Nakamura, Tomonori; Okamoto, Yuji; Nakagawa, Masanori; Takashima, Hiroshi

doi:10.1136/jnnp-2018-318839

Cited by 76 publications

(94 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[10][11][12][13][14][15][16] Nevertheless, there are limited data on the effect of targeted NGS panels on the genetic diagnosis of CMT in everyday clinical practice. [17][18][19][20] This study describes the effect of targeted NGS panels on the molecular diagnosis of CMT and related disorders in routine clinical practice in 2 specialized clinics in different health systems in the United Kingdom (London) and United States (Iowa).…”

mentioning

confidence: 99%

Targeted next-generation sequencing panels in the diagnosis of Charcot-Marie-Tooth disease

et al. 2020

View full text Add to dashboard Cite

ObjectiveTo investigate the effectiveness of targeted next-generation sequencing (NGS) panels in achieving a molecular diagnosis in Charcot-Marie-Tooth disease (CMT) and related disorders in a clinical setting.MethodsWe prospectively enrolled 220 patients from 2 tertiary referral centers, one in London, United Kingdom (n = 120), and one in Iowa (n = 100), in whom a targeted CMT NGS panel had been requested as a diagnostic test. PMP22 duplication/deletion was previously excluded in demyelinating cases. We reviewed the genetic and clinical data upon completion of the diagnostic process.ResultsAfter targeted NGS sequencing, a definite molecular diagnosis, defined as a pathogenic or likely pathogenic variant, was reached in 30% of cases (n = 67). The diagnostic rate was similar in London (32%) and Iowa (29%). Variants of unknown significance were found in an additional 33% of cases. Mutations in GJB1, MFN2, and MPZ accounted for 39% of cases that received genetic confirmation, while the remainder of positive cases had mutations in diverse genes, including SH3TC2, GDAP1, IGHMBP2, LRSAM1, FDG4, and GARS, and another 12 less common genes. Copy number changes in PMP22, MPZ, MFN2, SH3TC2, and FDG4 were also accurately detected. A definite genetic diagnosis was more likely in cases with an early onset, a positive family history of neuropathy or consanguinity, and a demyelinating neuropathy.ConclusionsNGS panels are effective tools in the diagnosis of CMT, leading to genetic confirmation in one-third of cases negative for PMP22 duplication/deletion, thus highlighting how rarer and previously undiagnosed subtypes represent a relevant part of the genetic landscape of CMT.

show abstract

mentioning

confidence: 99%

Targeted next-generation sequencing panels in the diagnosis of Charcot-Marie-Tooth disease

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The PMP22 duplication accounted for 66.7% of the genetically confirmed CMT cases and was responsible for 48.7% of all CMT patients in our cohort. The proportion of PMP22 duplication among CMT patients in Taiwan was higher than that in U.S., U.K., Germany, Spain and Japan (15–42%) . This phenomenon may come from ethnic differences.…”

Section: Discussionmentioning

confidence: 88%

“…The relatively high percentage of NEFL mutations in our CMT cohort (1.9%) with recurrent mutations of p.P8R and p.E396K (two and three pedigrees, respectively) suggested population‐specific founder effects of the NEFL mutations in Chinese population. NEFL mutations were also relatively prevalent in Japan, accounting for 0.9% and 2.3% of total CMT patients in two Japanese cohorts …”

Section: Discussionmentioning

confidence: 98%

“…Although a number of studies have investigated the frequencies and spectrum of mutations in one or some particular genes in CMT patients of different ethnicities, only a few provided a comprehensive landscape of the mutation spectrum and frequencies of multiple genes. Most of the studies were performed in Caucasian cohorts with CMT and two studies were conducted in the Japanese population . Except for a small‐scale study investigating 82 Chinese patients with CMT, no extensive mutational analysis has been performed in CMT patients of Han Chinese populations yet.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mutation spectrum of Charcot‐Marie‐Tooth disease among the Han Chinese in Taiwan

Hsu

Lin

Guo

et al. 2019

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective Charcot‐Marie‐Tooth disease (CMT) is a clinically and genetically heterogeneous group of inherited neuropathies. Mutations in more than 90 genes have been implicated in CMT; however, the mutational spectrum of CMT in Chinese population remains obscure. This study aims to provide a comprehensive overview of the frequency of mutations in Taiwanese patients with CMT and look for genotype‐phenotype correlations. Methods Mutational analyses were performed on 427 unrelated Taiwanese patients with CMT by polymorphic microsatellite markers analysis or real‐time fluorescent PCR for PMP22 duplication, Sanger sequencing for GJB1 mutations, and targeted sequencing covering 124 genes causing or relevant to inherited neuropathies. We also correlated the genotypes with the phenotypic features, such as age at disease onset and ulnar motor nerve conduction velocity. Results Pathogenic mutations were identified in 312 patients (73.1%; 312/427), including 208 patients with a PMP22 duplication, 40 patients with a GJB1 mutation, and 64 patients with a mutation in one of other 18 CMT genes. A confirmed molecular diagnosis was achieved in 84.4% (266/315) of the patients with demyelinating CMT and 41.1% (46/112) of the patients with axonal CMT. Mutations in MPZ, MFN2, or NEFL are the most frequent disease causes in patients with infantile‐onset CMT (≤2 years), while PMP22 duplications and mutations in GJB1, MFN2, or MPZ are the frequent causes among patients with childhood‐ or adolescence‐onset CMT (3–9 years). Interpretation This study provides a genotype‐phenotype landscape of CMT in Taiwan and highlights the unique spectrum of CMT genes frequencies among patients of Chinese origin.

show abstract

“…An estimate of CMT prevalence using data collected for 35 years [11] indicated that all CMT patients had not been diagnosed in Korea. Additionally, the observed increase in prevalence may be partly due to recent advances in molecular diagnosis, including next-generation sequencing, a method that has increased the rate of diagnosis among asymptomatic or mildly affected patients without a family history of CMT [15,16].…”

Section: Discussion/conclusionmentioning

confidence: 99%

Prevalence, Mortality, and Cause of Death in Charcot-Marie-Tooth Disease in Korea: A Nationwide, Population-Based Study

Park

Choi

et al. 2020

Neuroepidemiology

View full text Add to dashboard Cite

Background: Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous disorders that primarily affect the peripheral nervous system. Epidemiological studies of CMT have not yet been performed in Korea. Objectives: This study was performed to estimate the prevalence of CMT in Korea and the socioeconomic status, mortality, and causes of death of Korean patients with CMT. Methods: Data on patients with CMT were obtained from the rare intractable disease registry and the National Health Insurance Service for the years 2005–2018. Results: During the study period, 2,885 CMT patients were enrolled. The prevalence per 100,000 persons in 2018 was 5.2 (6.1 for men and 4.4 for women), peaking at ages 15–39 years, with almost twice as many men (n = 714) as women (n = 402) in this age group. Of the CMT patients, 226 (7.8%) were receiving medical aid, a public assistance program targeting poor individuals, at the time of diagnosis and 253 (8.8%) at last follow-up or death. From 2005 to 2017, 170 patients died, including 118 men and 52 women. The standardized mortality ratio (SMR) was 1.57 (95% CI 1.34–1.83) for all patients and did not differ in men and women. Age-specific SMR was highest in patients aged under 9 years, gradually declining thereafter. Neurologic disease as a cause of death was significantly more frequent in CMT patients than in the general population. Conclusions: This was the first nationwide epidemiologic study of CMT patients in Korea. This study confirmed the characteristics associated with the prevalence of and mortality from CMT by age and is the first to report the socioeconomic status and causes of death of CMT patients.

show abstract

Genetic profile and onset features of 1005 patients with Charcot-Marie-Tooth disease in Japan

Cited by 76 publications

References 27 publications

Targeted next-generation sequencing panels in the diagnosis of Charcot-Marie-Tooth disease

Targeted next-generation sequencing panels in the diagnosis of Charcot-Marie-Tooth disease

Mutation spectrum of Charcot‐Marie‐Tooth disease among the Han Chinese in Taiwan

Prevalence, Mortality, and Cause of Death in Charcot-Marie-Tooth Disease in Korea: A Nationwide, Population-Based Study

Contact Info

Product

Resources

About