Effectiveness of clinical exome sequencing in adult patients with difficult-to-diagnose neurological disorders

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Sainio , M T , Aaltio , J , Hyttinen , V , Kortelainen , M , Ojanen , S , Paetau , A , Tienari , P , Ylikallio , E , Auranen , M & Tyynismaa , H 2022 , ' Effectiveness of clinical exome sequencing in adult patients with difficult-to-diagnose neurological disorders ' , Acta Neurologica Scandinavica , vol. 145 , no. 1 , pp. 63-72 . https://doi.org/10.1111/ane.13522

Title: Effectiveness of clinical exome sequencing in adult patients with difficult-to-diagnose neurological disorders
Author: Sainio, Markus T.; Aaltio, Juho; Hyttinen, Virva; Kortelainen, Mika; Ojanen, Simo; Paetau, Anders; Tienari, Pentti; Ylikallio, Emil; Auranen, Mari; Tyynismaa, Henna
Contributor organization: STEMM - Stem Cells and Metabolism Research Program
Centre of Excellence in Stem Cell Metabolism
Faculty of Medicine
Veterinary Biosciences
University of Helsinki
Department of Pathology
Department of Neurosciences
HUS Neurocenter
Department of Medical and Clinical Genetics
Henna Tyynismaa / Principal Investigator
Date: 2022-01
Language: eng
Number of pages: 10
Belongs to series: Acta Neurologica Scandinavica
ISSN: 0001-6314
DOI: https://doi.org/10.1111/ane.13522
URI: http://hdl.handle.net/10138/340522
Abstract: Objectives Clinical diagnostics in adults with hereditary neurological diseases is complicated by clinical and genetic heterogeneity, as well as lifestyle effects. Here, we evaluate the effectiveness of exome sequencing and clinical costs in our difficult-to-diagnose adult patient cohort. Additionally, we expand the phenotypic and genetic spectrum of hereditary neurological disorders in Finland. Methods We performed clinical exome sequencing (CES) to 100 adult patients from Finland with neurological symptoms of suspected genetic cause. The patients were classified as myopathy (n = 57), peripheral neuropathy (n = 16), ataxia (n = 15), spastic paraplegia (n = 4), Parkinsonism (n = 3), and mixed (n = 5). In addition, we gathered the costs of prior diagnostic work-up to retrospectively assess the cost-effectiveness of CES as a first-line diagnostic tool. Results The overall diagnostic yield of CES was 27%. Pathogenic variants were found for 14 patients (in genes ANO5, CHCHD10, CLCN1, DES, DOK7, FKBP14, POLG, PYROXD1, SCN4A, TUBB3, and TTN) and likely pathogenic previously undescribed variants for 13 patients (in genes ABCD1, AFG3L2, ATL1, CACNA1A, COL6A1, DYSF, IRF2BPL, KCNA1, MT-ATP6, SAMD9L, SGCB, and TPM2). Age of onset below 40 years increased the probability of finding a genetic cause. Our cost evaluation of prior diagnostic work-up suggested that early CES would be cost-effective in this patient group, in which diagnostic costs increase linearly with prolonged investigations. Conclusions Based on our results, CES is a cost-effective, powerful first-line diagnostic tool in establishing the molecular diagnosis in adult neurological patients with variable symptoms. Importantly, CES can markedly shorten the diagnostic odysseys of about one third of patients.
Subject: clinical exome sequencing
cost analysis
neurological disease
3124 Neurology and psychiatry
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion

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