Improving diagnosis of inherited peripheral neuropathies through gene panel analysis
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Improving diagnosis of inherited peripheral neuropathies through gene panel analysis Petra Laššuthová1*, Dana Šafka Brožková1, Marcela Krůtová1, Jana Neupauerová1, Jana Haberlová2, Radim Mazanec3, Pavel Dřímal1 and Pavel Seeman1
Abstract Background: Inherited peripheral neuropathies (IPN) are the most common inherited neurological condition. It represents a highly heterogeneous group, both clinically and genetically. Targeted disease specific gene panel massively parallel sequencing (MPS) seems to be a useful tool in diagnosis of disorders with high genetic heterogeneity. Methods: In our study, we have designed, validated and updated our own custom gene panel of all known genes associated with IPN. One hundred and ninety-eight patients have been tested so far. Only patients in whom mutations in more common causes or relevant genes have already been excluded were enrolled. Five consecutive panel designs were prepared according to recent literature search, the last one covering ninety-three genes. Each patient was tested only once. All data were evaluated with at least two different pipelines. Results: In summary, causative mutation has been found in fifty-one patients (26 %). The results were inconclusive in thirty-one (16 %) patients. No variants of likely significance to IPN were found in one hundred and sixteen (58 %) patients. Conclusion: MPS gene panel enables testing of all known IPN causes at once with high coverage and at an affordable cost making it truly a method of choice also in IPN. Gene panel testing results in several interesting results and findings. Keywords: Inherited peripheral neuropathies, Charcot-Marie-Tooth, Targeted gene panel testing, Mutation, Phenotype Abbreviations: CMT, Charcot-Marie-Tooth; IPN, Inherited peripheral neuropathies; WES, Whole exome sequencing
Background Inherited peripheral neuropathies (IPN) are the most common inherited neurological condition, with a reported prevalence 1/2500 [1]; a prevalence 1/1214 has also been noted [2]. IPN is an example of a genetically highly heterogeneous group of disorders. Mutations in more than 90 genes are already associated with IPN [3, 4]. Our Center for inherited neuropathies in Charles University in Prague and University Hospital Motol is unique for the whole Czech Republic. In the course of 17 years, we have collected DNA samples and clinical * Correspondence: [email protected] 1 Department of Paediatric Neurology, DNA Laboratory, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic Full list of author information is available at the end of the article
data from more than 3100 patients from 2155 independent families. The cause of inherited neuropathy has been stated in 920 unrelated families (1775 patients), so far. In the previously diagnosed 920 families, PMP22 duplication was detected in 412 families (772 patients), PMP22 deletions were detected in 290 families (485 patients) and in the remaining 218 families (518 patients) causative point mutation
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