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Bonnet, Céline; Pellerin, David; Roth, Virginie; Clément, Guillemette; Wandzel, Marion; Lambert, Laëtitia; Frismand, Solène; Douarinou, Marian; Grosset, Anais; Bekkour, Ines; Weber, Frédéric; Girardier, Florent; Robin, Clément; Cacciatore, Stéphanie; Bronner, Myriam; Pourié, Carine; Dreumont, Natacha; Puisieux, Salomé; Iruzubieta, Pablo; Dicaire, Marie-Josée; Evoy, François; Rioux, Marie-France; Hocquel, Armand; La Piana, Roberta; [...]

Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia/spinocerebellar ataxia 27B

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  • Medientyp: E-Artikel
  • Titel: Optimized testing strategy for the diagnosis of GAA-FGF14 ataxia/spinocerebellar ataxia 27B
  • Beteiligte: Bonnet, Céline; Pellerin, David; Roth, Virginie; Clément, Guillemette; Wandzel, Marion; Lambert, Laëtitia; Frismand, Solène; Douarinou, Marian; Grosset, Anais; Bekkour, Ines; Weber, Frédéric; Girardier, Florent; Robin, Clément; Cacciatore, Stéphanie; Bronner, Myriam; Pourié, Carine; Dreumont, Natacha; Puisieux, Salomé; Iruzubieta, Pablo; Dicaire, Marie-Josée; Evoy, François; Rioux, Marie-France; Hocquel, Armand; La Piana, Roberta; [...]
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: Scientific Reports
  • Sprache: Englisch
  • DOI: 10.1038/s41598-023-36654-8
  • ISSN: 2045-2322
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Dominantly inherited GAA repeat expansions in <jats:italic>FGF14</jats:italic> are a common cause of spinocerebellar ataxia (GAA-<jats:italic>FGF14</jats:italic> ataxia; spinocerebellar ataxia 27B). Molecular confirmation of <jats:italic>FGF14</jats:italic> 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 <jats:italic>FGF14</jats:italic> 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 products significantly underestimated expansion sizes compared to nanopore sequencing (slope, 0.87 [95% CI, 0.81 to 0.93]; intercept, 14.58 [95% CI, − 2.48 to 31.12]) and gel electrophoresis (slope, 0.84 [95% CI, 0.78 to 0.97]; intercept, 21.34 [95% CI, − 27.66 to 40.22]). 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 to 1.04]; intercept: 10.62 [95% CI, − 7.49 to 27.71]), and gel electrophoresis (slope: 0.94 [95% CI, 0.88 to 1.09]; intercept: 18.81 [95% CI, − 41.93 to 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 <jats:italic>FGF14</jats:italic> (GAA)<jats:sub>≥250</jats:sub> expansion. This novel strategy reliably detected and sized <jats:italic>FGF14</jats:italic> GAA expansions, and compared favorably to long-read sequencing.</jats:p>
  • Zugangsstatus: Freier Zugang