Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variabilityReport as inadecuate




Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variability - Download this document for free, or read online. Document in PDF available to download.

BMC Medical Genetics

, 16:84

First Online: 21 September 2015Received: 17 April 2015Accepted: 21 August 2015

Abstract

BackgroundInherited peripheral neuropathy IPN is a clinically and genetically heterogeneous group of disorders with more than 90 genes associated with the different subtypes. Sequential gene screening is gradually being replaced by next generation sequencing NGS applications.

MethodsWe designed and validated a targeted NGS panel assay including 56 genes associated with known causes of IPN. We report our findings following NGS panel testing of 448 patients with different types of clinically-suspected IPN.

ResultsGenetic diagnosis was achieved in 137 patients 31 % and involved 195 pathogenic variants in 31 genes. 93 patients had pathogenic variants in genes where a resulting phenotype follows dominant inheritance, 32 in genes where this would follow recessive inheritance, and 12 presented with X-linked disease.

Almost half of the diagnosed patients 64 had a pathogenic variant either in genes not previously available for routine diagnostic testing in a UK laboratory 50 patients or in genes whose primary clinical association was not IPN 14.

Seven patients had a pathogenic variant in a gene not hitherto indicated from their phenotype and three patients had more than one pathogenic variant, explaining their complex phenotype and providing information essential for accurate prediction of recurrence risks.

ConclusionsOur results demonstrate that targeted gene panel testing is an unbiased approach which overcomes the limitations imposed by limited existing knowledge for rare genes, reveals high heterogeneity, and provides high diagnostic yield. It is therefore a highly efficient and cost effective tool for achieving a genetic diagnosis for IPN.

Electronic supplementary materialThe online version of this article doi:10.1186-s12881-015-0224-8 contains supplementary material, which is available to authorized users.

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Author: Thalia Antoniadi - Chris Buxton - Gemma Dennis - Natalie Forrester - Debbie Smith - Peter Lunt - Sarah Burton-Jones

Source: https://link.springer.com/



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