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Charcot‐Marie‐Tooth disease: Genetic profile of patients from a large Brazilian neuromuscular reference center
Author(s) -
Uchôa Cavalcanti Eduardo Boiteux,
Santos Savana Camilla de Lima,
Martins Carlos Eduardo Speck,
Carvalho Daniel Rocha,
Rizzo Isabela Maria Pinto de Oliveira,
Freitas Maria Cristina Del Negro Barroso,
Silva Freitas Denise,
Souza Francineide Sadala,
Junior Altamir Monteiro,
Nascimento Osvaldo José Moreira
Publication year - 2021
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/jns.12458
Subject(s) - proband , sanger sequencing , medicine , multiplex ligation dependent probe amplification , gene duplication , disease , population , epidemiology , mutation , genetics , gene , biology , environmental health , exon
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.