Argentinian clinical genomics in a leukodystrophies and genetic leukoencephalopathies cohort: Diagnostic yield in our first 9 years.


Journal

Annals of human genetics
ISSN: 1469-1809
Titre abrégé: Ann Hum Genet
Pays: England
ID NLM: 0416661

Informations de publication

Date de publication:
01 2020
Historique:
received: 26 12 2018
revised: 27 02 2019
accepted: 18 07 2019
pubmed: 17 8 2019
medline: 4 2 2021
entrez: 17 8 2019
Statut: ppublish

Résumé

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. 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. 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. 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.

Identifiants

pubmed: 31418856
doi: 10.1111/ahg.12345
doi:

Substances chimiques

Biomarkers 0

Types de publication

Journal Article Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

11-28

Subventions

Organisme : "Lautaro te Necesita" Foundation
Pays : International
Organisme : Ministry of Science and Technology of Argentina
Pays : International
Organisme : Fund for Scientific and Technological Research
Pays : International

Informations de copyright

© 2019 John Wiley & Sons Ltd/University College London.

Références

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Auteurs

Leila Cohen (L)

Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Analisa Manín (A)

Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Nancy Medina (N)

Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Sergio Rodríguez-Quiroga (S)

Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
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.

Dolores González-Morón (D)

Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Neuroophthalmology Section, Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Julieta Rosales (J)

Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Hernan Amartino (H)

Child Neurology Department, Hospital Universitario Austral, Buenos Aires, Argentina.

Norma Specola (N)

Metabolism Department, Hospital de Niños "Sor María Ludovica" de La Plata, Buenos Aires, Argentina.

Marta Córdoba (M)

Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Marcelo Kauffman (M)

Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Instituto de Investigaciones en Medicina Traslacional-CONICET y Facultad de Ciencias Biomédicas-Universidad Austral, Buenos Aires, Argentina.

Patricia Vega (P)

Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mejía, CABA, Centro Universitario de Neurología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

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