Abstract Details

Title Charcot-Marie-Tooth disease: genetic profile of 500 patients from a large Brazilian neuromuscular center

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) Neuromuscular and Clinical Neurophysiology (EMG) Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 135

Objective To estimate frequency of different mutations in Brazilian patients evaluated in a neuromuscular center and compare our data with previously published studies findings.

Background Charcot-Marie-Tooth disease (CMT), also known as hereditary sensory-motor neuropathy, is the most common inherited neuromuscular disorder, with a prevalence ranging from 1: 2500 to 1:10:000. More than 90 genes have been associated with CMT. Despite the genetic heterogeneity underlying this disorder, approximately 90% of all genetically confirmed cases among different series are due to mutations in only four genes: PMP22, GJB1, MPZ, and MFN2. In Brazil, we only have epidemiological data about CMT1A and CMTX1. A more detailed profile would give a better understanding of CMT in our country.

Design/Methods From February 2015 to July 2020 we evaluated 500 patients with suspected hereditary sensory-motor neuropathy. Diagnosis of CMT were based on the presence of slowly progressive sensory-motor neuropathy, independently of family history, and after exclusion of common causes of acquired neuropathy. CMT subtype was classified according to conduction velocity of median or ulnar nerve (< 38 m/s demyelinating and ≥ 38 m/s axonal). MLPA technique to access duplication/deletion mutations of PMP22 gene and Sanger sequencing of GJB1 gene were performed in all cases suspected of demyelinating CMT. All negative cases were evaluated by a targeted gene panel sequencing (75 genes).

Results We identified pathogenic or likely pathogenic variants in 378 cases. In patients with identified mutations, the most common causative genes were PMP22 [duplication] (n = 222, 58.73%), GBJ1 (n = 76, 20.1%), MPZ (n = 14, 3.7%), MFN2 (n = 10, 2.64%), GDAP1 (n = 7, 1.85%). All other identified variants respond for less than 1% of the cases.

Conclusions This study provides further data about frequency of CMT subtypes in a Brazilian clinical-based population and highlights the importance of rarer and previously undiagnosed variants for the clinical practice.

Authors/Disclosures
Eduardo B. Uchoa Cavalcanti, MD, PhD, MSc, F�鶹��ýӳ�� (Hospital Sarah - Lago Norte - Brasília) PRESENTER	Dr. Uchoa Cavalcanti has nothing to disclose.
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Osvaldo J. Nascimento, MD, PhD, F�鶹��ýӳ�� (Fluminense Federal University)	Dr. Nascimento has nothing to disclose.

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