Whole-exome sequencing is a valuable diagnostic tool for inherited peripheral neuropathies: Outcomes from a cohort of 50 families
| Autor: | Steven K. Baker, Meredith K. Gillespie, Mark A. Tarnopolsky, Brenda McInnes, Dennis E. Bulman, David A. Dyment, Lauren Brady, Justin D. Wagner, Pierre R. Bourque, Jillian S. Parboosingh, Jacek Majewski, Christopher Smith, Martine Tétreault, Gabriella Horvath, Eric Bareke, J Warman-Chardon, Grace Yoon, Francois P. Bernier, Kym M. Boycott, Allan Micheil Innes, Cynthia J. Curry, Taila Hartley |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Candidate gene Kinesins Context (language use) Disease Biology Protein Serine-Threonine Kinases Bioinformatics 03 medical and health sciences 0302 clinical medicine Acetyltransferases Charcot-Marie-Tooth Disease Exome Sequencing Genetics medicine Humans Exome Genetics (clinical) Exome sequencing KIF1A Genetic heterogeneity Intracellular Signaling Peptides and Proteins High-Throughput Nucleotide Sequencing Peripheral Nervous System Diseases medicine.disease 3. Good health 030104 developmental biology Peripheral neuropathy Mutation Female Hereditary motor and sensory neuropathy 030217 neurology & neurosurgery |
| Zdroj: | Clinical genetics. 93(2) |
| ISSN: | 1399-0004 |
| Popis: | The inherited peripheral neuropathies (IPNs) are characterized by marked clinical and genetic heterogeneity and include relatively frequent presentations such as Charcot-Marie-Tooth disease and hereditary motor neuropathy, as well as more rare conditions where peripheral neuropathy is associated with additional features. There are over 250 genes known to cause IPN-related disorders but it is estimated that in approximately 50% of affected individuals a molecular diagnosis is not achieved. In this study, we examine the diagnostic utility of whole-exome sequencing (WES) in a cohort of 50 families with 1 or more affected individuals with a molecularly undiagnosed IPN with or without additional features. Pathogenic or likely pathogenic variants in genes known to cause IPN were identified in 24% (12/50) of the families. A further 22% (11/50) of families carried sequence variants in IPN genes in which the significance remains unclear. An additional 12% (6/50) of families had variants in novel IPN candidate genes, 3 of which have been published thus far as novel discoveries (KIF1A, TBCK, and MCM3AP). This study highlights the use of WES in the molecular diagnostic approach of highly heterogeneous disorders, such as IPNs, places it in context of other published neuropathy cohorts, while further highlighting associated benefits for discovery. |
| Databáze: | OpenAIRE |
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