Diagnostic yield of targeted sequential and massive panel approaches for inherited neuropathies
Autor: | Carolina Serpa Brasil, Alice Maria Luderitz Hoefel, Jonas Alex Morales Saute, Janice Pacheco Dias Padilha, Pablo Brea Winckler, Karina Carvalho Donis, Ana Carolina Brusius-Facchin |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Oncology Adult Male congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Disease 030105 genetics & heredity DNA sequencing Connexins Inherited neuropathies 03 medical and health sciences symbols.namesake Charcot-Marie-Tooth Disease Internal medicine Epidemiology Genetics medicine Possible diagnosis Humans Multiplex ligation-dependent probe amplification Pathology Molecular Genetics (clinical) Sanger sequencing business.industry Sequence Analysis DNA nervous system diseases 030104 developmental biology Mutation symbols Female business Multiplex Polymerase Chain Reaction Myelin P0 Protein Brazil Myelin Proteins |
Zdroj: | Clinical geneticsREFERENCES. 98(2) |
ISSN: | 1399-0004 |
Popis: | Diagnostic yield of genetic studies for Charcot-Marie-Tooth disease (CMT) is little known, with a lack of epidemiological data to build better diagnostic strategies outside the United States and Europe. We aimed to evaluate the performance of two molecular diagnostic strategies for patients with CMT, and to characterize epidemiological findings of these conditions in southern Brazil. We performed a single-center cross-sectional study, in which 94 patients (55 families) with CMT suspicion were evaluated. Overall, the diagnostic yield of the combined strategy of Multiplex-ligation-dependent-probe-amplification (MLPA) of PMP22/GJB1/MPZ and GJB1/MPZ/PMP22 Sanger sequencing was 63.6% (28/44) for index cases with demyelinating/intermediate CMT suspicion (21 CMT1A-PMP22, 5 CMTX1-GJB1 and 2 with probably CMT1B-MPZ diagnosis). Five of the 11 index cases (45.4%) with axonal CMT had at least a possible diagnosis with next generation sequencing (NGS) panel of 104 inherited neuropathies-related genes (one each with CMT1A-PMP22, CMT2A-MFN2, CMT2K-GDAP1, CMT2U-MARS, CMT2W-HARS1). Detailed clinical, neurophysiological and molecular data of families are provided. Sequential molecular diagnosis strategies with MLPA plus target Sanger sequencing for demyelinating/intermediate CMT had high diagnostic yield, and almost half of axonal CMT families had at least a possible diagnosis with the comprehensive NGS panel. Most frequent subtypes of CMT in our region are CMT1A-PMP22 and CMTX1-GJB1. |
Databáze: | OpenAIRE |
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