Charcot‐Marie‐Tooth disease: Genetic profile of patients from a large Brazilian neuromuscular reference center

Abstract

This study aimed to describe the clinical, genetic, and epidemiological features of Charcot-Marie-Tooth disease (CMT) in Brazilian patients from a tertiary center, and to compare our data with previously published findings. This retrospective observational study conducted between February 2015 and July 2020 evaluated 503 patients (94 families and 192 unrelated individuals), diagnosed with CMT. Clinical and neurophysiological data were obtained from electronic medical records and blood samples were used for genetic analyses. Multiplex ligation-dependent probe amplification was used to assess duplications/deletions in PMP22. Sanger sequencing of GJB1 was performed in cases of suspected demyelinating CMT. Targeted gene panel sequencing was used for the remaining negative demyelinating cases and all axonal CMT cases. The first decade of life was the most common period of disease onset. In all, 353 patients had demyelinating CMT, 39 had intermediate CMT, and 111 had axonal CMT. Pathogenic or likely pathogenic variants were identified in 197 index cases.The most common causative genes among probands were PMP22 (duplication) (n = 116, 58.88%), GJB1 (n = 23, 11.67%), MFN2 (n = 12, 6.09%), GDAP1 (n = 7, 3.55%), MPZ (n = 6, 3.05%), PMP22 (point mutation) (n = 6, 3.05%), NEFL (n = 3, 1.52%), SBF2 (n = 3, 1.52%), and SH3TC2 (n = 3, 1.52%). Other identified variants were ≤1% of index cases. This study provides further data on the frequency of CMT subtypes in a Brazilian clinical-based population and highlights the importance of rarer and previously undiagnosed variants in clinical practice.

Variants of aminoacyl‐tRNA synthetase genes in Charcot‐Marie‐Tooth disease: A Korean cohort study

“…The frequencies of CMT patients with ARS gene mutations were dependent on the ethnic groups, although the numbers of study groups and patients were limited. The frequency of the total Korean CMT cases with ARS gene mutations was slightly higher than that observed in Han Chinese (Taiwan) (0.70%), 30 Italian (0.35%), 31 Brazilian (0.35%), 35 and Hungarian populations (0.00%) 33 . In patients excluding CMT1A cases, the frequencies in the Korean population were also higher than those of most other populations, such as the Japanese (1.29%), 32 Han Chinese (1.37%), 30 Italian (0.60%), 31 and Brazilian (0.59%) 35 .…”

“…The frequency of the total Korean CMT cases with ARS gene mutations was slightly higher than that observed in Han Chinese (Taiwan) (0.70%), 30 Italian (0.35%), 31 Brazilian (0.35%), 35 and Hungarian populations (0.00%) 33 . In patients excluding CMT1A cases, the frequencies in the Korean population were also higher than those of most other populations, such as the Japanese (1.29%), 32 Han Chinese (1.37%), 30 Italian (0.60%), 31 and Brazilian (0.59%) 35 . However, the frequencies of British (London) and American (Iowa) populations were slightly higher than that of the Korean population 34 …”

“…33 In patients excluding CMT1A cases, the frequencies in the Korean population were also higher than those of most other populations, such as the Japanese (1.29%), 32 Han Chinese (1.37%), 30 Italian (0.60%), 31 and Brazilian (0.59%). 35 However, the frequencies of British (London) and American (Iowa) populations were slightly higher than that of the Korean population. 34 We also observed many rare or novel ARS gene variants that were not considered as genetic causes of the disease.…”

Comprehensive Genetic Analyses of Inherited Peripheral Neuropathies in Japan: Making Early Diagnosis Possible

“…These top three genes are comparable to the findings of several other countries; however, GJB1, rather than MFN2, is the most common in their studies. This may be related to the predominance of axonal subtypes of IPNs in the current analysis, similar to Norway, but distinct from other countries, wherein demyelinating subtypes had predominance (1.1-3.18:1) [9,[14][15][16][17][18][19][20][21][22][23]27,29]. The reason for this phenomenon may be associated with the PMP22 CNV exclusion or as a regional characteristic.…”

Genetic and Clinical Studies of Peripheral Neuropathies with Three Small Heat Shock Protein Gene Variants in Korea

“…When the frequency in the patients excluding CMT1A was compared with other study groups, it was similar with 1.59% of Japanese [ 10 ]. It was higher than the frequencies of Han Chinese (0.91%), British (0.83%), American (0.00%), and Brazilian (0.00%), while lower than those of Italian (4.80%) and Spanish (3.94%) [ 8 , 9 , 34 , 35 , 36 ].…”