Abstract Details

Title NGS as a diagnostic tool for CMT Disease: The experience at Sarah Network of Rehabilitation Hospitals

Topic Neuromuscular and Clinical Neurophysiology (EMG)

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

Poster/Presentation
Number 081

Objective

To investigate the effectiveness of targetered next-generation sequencing (NGS) panels in achieving a molecular diagnosis in Charcot-Marie-Tooth disease (CMT) in a clinical setting.

Background 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 Latin America, we have limited data about the effect of NGS panels on the genetic diagnosis of CMT in clinical practice.

Design/Methods Next-generation sequencing (NGS) was performed by the Molecular Biology Laboratory in 327 patients with suspected hereditary sensory-motor neuropathy who did not have mutations on PMP22 and GJB1 genes. Enrichment was performed with a Custom SureSelect QXT Panel with 69 genes previously associated to HSMN. The sequences were analyzed in the Alissa software (v5.3) and variants were classified according to ACMG recommendations.

Results Molecular diagnosis was possible in 95 patients (29%) and variants classified as VUS were identified in 105 patients (32%). We did not find variants in the remaining 127 patients (39%). 50 out of 95 patients (52%) in which molecular diagnosis was possible presented variants in genes associated to demyelinating CMT, 30 out of 95 patients (32%) presented variants in genes associated to axonal CMT and 15 out of 95 patients (16%) presented variants in genes associated to other subtypes of CMT.

Conclusions NGS improved the molecular diagnostic rate, allowing the definition of molecular pathology in 29% of cases. Most importantly, NGS analysis allowed finding novel mutations. This study provides further evidence that NGS panel are an effective tool to define the molecular diagnosis in CMT patients in a clinical setting.

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.
	No disclosure on file
	No disclosure on file
	No disclosure on file

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