Argentinian clinical genomics in a leukodystrophies and genetic leukoencephalopathies cohort: Diagnostic yield in our first 9 years. (16th August 2019)

• Record Type: Journal Article
• Authors: Cohen, Leila; Manín, Analisa; Medina, Nancy; Rodríguez‐Quiroga, Sergio; González‐Morón, Dolores; Rosales, Julieta; Amartino, Hernan; Specola, Norma; Córdoba, Marta; Kauffman, Marcelo; Vega, Patricia
• Is Part Of: Annals of human genetics. Volume 84:Number 1(2020:Jan.)
• Page Start: 11
• Page End: 28
• Publication Date: 2019-08-16
• Subjects: diagnostic procedure -- genetic leukoencephalopathies -- leukodystrophies -- next‐generation sequencing; Human genetics -- Periodicals; 599.935
• DOI: 10.1111/ahg.12345
• Languages: English
• ISSNs: 0003-4800

Abstract

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.