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Molecular confirmation of\n                    <jats:italic>FGF14<\/jats:italic>\n                    GAA repeat expansions has thus far mostly relied on long-read sequencing, a technology that is not yet widely available in clinical laboratories. We developed and validated a strategy to detect\n                    <jats:italic>FGF14<\/jats:italic>\n                    GAA repeat expansions using long-range PCR, bidirectional repeat-primed PCRs, and Sanger sequencing. We compared this strategy to targeted nanopore sequencing in a cohort of 22 French Canadian patients and next validated it in a cohort of 53 French index patients with unsolved ataxia. Method comparison showed that capillary electrophoresis of long-range PCR amplification\u00a0products significantly underestimated expansion sizes compared to nanopore sequencing (slope, 0.87 [95% CI, 0.81\u00a0to 0.93]; intercept, 14.58 [95% CI, \u2212\u00a02.48\u00a0to\u00a031.12]) and gel electrophoresis (slope, 0.84 [95% CI, 0.78\u00a0to\u00a00.97]; intercept, 21.34 [95% CI, \u2212\u00a027.66\u00a0to\u00a040.22]). The latter techniques yielded similar size estimates. Following calibration with internal controls, expansion size estimates were similar between capillary electrophoresis and nanopore sequencing (slope: 0.98 [95% CI, 0.92\u00a0to\u00a01.04]; intercept: 10.62 [95% CI, \u2212\u00a07.49\u00a0to\u00a027.71]), and gel electrophoresis (slope: 0.94 [95% CI, 0.88\u00a0to\u00a01.09]; intercept: 18.81 [95% CI, \u2212\u00a041.93\u00a0to 39.15]). Diagnosis was accurately confirmed for all 22 French Canadian patients using this strategy. We also identified 9 French patients (9\/53; 17%) and 2 of their relatives who carried an\n                    <jats:italic>FGF14<\/jats:italic>\n                    (GAA)\n                    <jats:sub>\u2265250<\/jats:sub>\n                    expansion. This novel strategy reliably detected and sized\n                    <jats:italic>FGF14<\/jats:italic>\n                    GAA expansions, and compared favorably to long-read sequencing.\n                  <\/jats:p>","DOI":"10.1038\/s41598-023-36654-8","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T15:02:13Z","timestamp":1686841333000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia\/spinocerebellar ataxia 27B"],"prefix":"10.1038","volume":"13","author":[{"given":"C\u00e9line","family":"Bonnet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pellerin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillemette","family":"Cl\u00e9ment","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Wandzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La\u00ebtitia","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol\u00e8ne","family":"Frismand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Douarinou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anais","family":"Grosset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Bekkour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Girardier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9ment","family":"Robin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Cacciatore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Bronner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Pouri\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natacha","family":"Dreumont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salom\u00e9","family":"Puisieux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Iruzubieta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jos\u00e9e","family":"Dicaire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Evoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-France","family":"Rioux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armand","family":"Hocquel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"La Piana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthis","family":"Synofzik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt C.","family":"Danzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Zuchner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Brais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Renaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"36654_CR1","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1212\/WNL.0000000000004311","volume":"89","author":"I Giordano","year":"2017","unstructured":"Giordano, I. et al. 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Stephan Zuchner is consultant on drug targets for Aeglea BioTherapeutics and consultant on clinical trial design for Applied Therapeutics, all of them unrelated to the work in the present manuscript. Other authors have no relevant financial interests to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"9737"}}