Leila Cohen1, Analisa Manín1, Nancy Medina1,2, Sergio Rodríguez-Quiroga1,2,3, Dolores González-Morón1,2,4, Julieta Rosales1,2, Hernan Amartino5, Norma Specola6, Marta Córdoba1,2, Marcelo Kauffman1,2,7, Patricia Vega2. 1. Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. 2. Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. 3. Movements Disorders Section, Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. 4. Neuroophthalmology Section, Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. 5. Child Neurology Department, Hospital Universitario Austral, Buenos Aires, Argentina. 6. Metabolism Department, Hospital de Niños "Sor María Ludovica" de La Plata, Buenos Aires, Argentina. 7. Instituto de Investigaciones en Medicina Traslacional-CONICET y Facultad de Ciencias Biomédicas-Universidad Austral, Buenos Aires, Argentina.
Abstract
INTRODUCTION AND OBJECTIVES: Leukodystrophies and genetic leukoencephalopathies constitute a vast group of pathologies of the cerebral white matter. The large number of etiopathogenic genes and the frequent unspecificity on the clinical-radiological presentation generate remarkable difficulties in the diagnosis approach. Despite recent and significant developments, molecular diagnostic yield is still less than 50%. Our objective was to develop and explore the usefulness of a new diagnostic procedure using standardized molecular diagnostic tools, and next-generation sequencing techniques. MATERIALS AND METHODS: A prospective, observational, analytical study was conducted in a cohort of 46 patients, evaluated between May 2008 and December 2016, with a suspected genetic leukoencephalopathy or leukodystrophy. A diagnostic procedure was set up using classical monogenic tools in patients with characteristic phenotypes, and next-generation techniques in nonspecific ones. RESULTS: Global diagnostic procedure yield was 57.9%, identifying the etiological pathogenesis in 22 of the 38 studied subjects. Analysis by subgroups, Sanger method, and next-generation sequencing showed a yield of 64%, and 46.1% respectively. The most common pathologies were adrenoleukodystrophy, cerebral autosomal-dominant arteriopathy with subcortical infarcts (CADASIL), and vanishing white matter disease. CONCLUSIONS: Our results confirm the usefulness of the proposed diagnostic procedure expressed in a high diagnostic yield and suggest a more optimal cost-effectiveness in an etiological analysis phase.
INTRODUCTION AND OBJECTIVES:Leukodystrophies and genetic leukoencephalopathies constitute a vast group of pathologies of the cerebral white matter. The large number of etiopathogenic genes and the frequent unspecificity on the clinical-radiological presentation generate remarkable difficulties in the diagnosis approach. Despite recent and significant developments, molecular diagnostic yield is still less than 50%. Our objective was to develop and explore the usefulness of a new diagnostic procedure using standardized molecular diagnostic tools, and next-generation sequencing techniques. MATERIALS AND METHODS: A prospective, observational, analytical study was conducted in a cohort of 46 patients, evaluated between May 2008 and December 2016, with a suspected genetic leukoencephalopathy or leukodystrophy. A diagnostic procedure was set up using classical monogenic tools in patients with characteristic phenotypes, and next-generation techniques in nonspecific ones. RESULTS: Global diagnostic procedure yield was 57.9%, identifying the etiological pathogenesis in 22 of the 38 studied subjects. Analysis by subgroups, Sanger method, and next-generation sequencing showed a yield of 64%, and 46.1% respectively. The most common pathologies were adrenoleukodystrophy, cerebral autosomal-dominant arteriopathy with subcortical infarcts (CADASIL), and vanishing white matter disease. CONCLUSIONS: Our results confirm the usefulness of the proposed diagnostic procedure expressed in a high diagnostic yield and suggest a more optimal cost-effectiveness in an etiological analysis phase.
Authors: Agatha Schlüter; Agustí Rodríguez-Palmero; Edgard Verdura; Valentina Vélez-Santamaría; Montserrat Ruiz; Stéphane Fourcade; Laura Planas-Serra; Juan José Martínez; Cristina Guilera; Marisa Girós; Rafael Artuch; María Eugenia Yoldi; Mar O'Callaghan; Angels García-Cazorla; Judith Armstrong; Itxaso Marti; Elisabet Mondragón Rezola; Claire Redin; Jean Louis Mandel; David Conejo; Concepción Sierra-Córcoles; Sergi Beltrán; Marta Gut; Elida Vázquez; Mireia Del Toro; Mónica Troncoso; Luis A Pérez-Jurado; Luis G Gutiérrez-Solana; Adolfo López de Munain; Carlos Casasnovas; Sergio Aguilera-Albesa; Alfons Macaya; Aurora Pujol Journal: Neurology Date: 2022-01-10 Impact factor: 9.910