{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:32:31Z","timestamp":1790839951467,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T00:00:00Z","timestamp":1513036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000092","name":"Ontario Genomics Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>The inherited peripheral neuropathies (<jats:styled-content style=\"fixed-case\">IPNs<\/jats:styled-content>) are characterized by marked clinical and genetic heterogeneity and include relatively frequent presentations such as Charcot\u2010Marie\u2010Tooth 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 <jats:styled-content style=\"fixed-case\">IPN<\/jats:styled-content>\u2010related 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\u2010exome sequencing (<jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content>) in a cohort of 50 families with 1 or more affected individuals with a molecularly undiagnosed <jats:styled-content style=\"fixed-case\">IPN<\/jats:styled-content> with or without additional features. Pathogenic or likely pathogenic variants in genes known to cause <jats:styled-content style=\"fixed-case\">IPN<\/jats:styled-content> were identified in 24% (12\/50) of the families. A further 22% (11\/50) of families carried sequence variants in <jats:styled-content style=\"fixed-case\">IPN<\/jats:styled-content> genes in which the significance remains unclear. An additional 12% (6\/50) of families had variants in novel <jats:styled-content style=\"fixed-case\">IPN<\/jats:styled-content> candidate genes, 3 of which have been published thus far as novel discoveries (<jats:italic><jats:styled-content style=\"fixed-case\">KIF1A<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">TBCK<\/jats:styled-content><\/jats:italic>, and <jats:italic><jats:styled-content style=\"fixed-case\">MCM3AP<\/jats:styled-content><\/jats:italic>). This study highlights the use of <jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content> in the molecular diagnostic approach of highly heterogeneous disorders, such as <jats:styled-content style=\"fixed-case\">IPNs<\/jats:styled-content>, places it in context of other published neuropathy cohorts, while further highlighting associated benefits for discovery.<\/jats:p>","DOI":"10.1111\/cge.13101","type":"journal-article","created":{"date-parts":[[2017,7,14]],"date-time":"2017-07-14T13:46:41Z","timestamp":1500040001000},"page":"301-309","source":"Crossref","is-referenced-by-count":55,"title":["Whole\u2010exome sequencing is a valuable diagnostic tool for inherited peripheral neuropathies: Outcomes from a cohort of 50 families"],"prefix":"10.1111","volume":"93","author":[{"given":"T.","family":"Hartley","sequence":"first","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.D.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Warman\u2010Chardon","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa  Ottawa Canada"},{"name":"Department of Genetics Children's Hospital of Eastern Ontario  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"T\u00e9treault","sequence":"additional","affiliation":[{"name":"Department of Human Genetics McGill University  Montr\u00e9al Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Brady","sequence":"additional","affiliation":[{"name":"Department of Pediatrics McMaster University Medical Centre  Hamilton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Medicine McMaster University Medical Centre  Hamilton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Tarnopolsky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics McMaster University Medical Centre  Hamilton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.R.","family":"Bourque","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.S.","family":"Parboosingh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Cumming School of Medicine University of Calgary  Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Cumming School of Medicine University of Calgary  Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"McInnes","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Cumming School of Medicine University of Calgary  Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.M.","family":"Innes","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Cumming School of Medicine University of Calgary  Calgary Canada"},{"name":"Alberta Children's Hospital Research Institute University of Calgary  Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Bernier","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Cumming School of Medicine University of Calgary  Calgary Canada"},{"name":"Alberta Children's Hospital Research Institute University of Calgary  Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.J.","family":"Curry","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California  San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Yoon","sequence":"additional","affiliation":[{"name":"Divisions of Neurology and Clinical and Metabolic Genetics, The Hospital for Sick Children University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.A.","family":"Horvath","sequence":"additional","affiliation":[{"name":"Division of Biochemical Diseases, Department of Pediatrics, B.C. 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