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New generation genetic testing entering the clinic

Gorcenco, Sorina LU ; Ilinca, Andreea LU ; Almasoudi, Wejdan LU ; Kafantari, Efthymia LU ; Lindgren, Arne G. LU and Puschmann, Andreas LU (2020) In Parkinsonism and Related Disorders 73. p.72-84
Abstract

New generation sequencing (NGS) genetic testing is a powerful diagnostic tool and is increasingly used in the clinical workup of patients, especially in unusual presentations or where a positive family history suggests heritable disease. This review addresses the NGS technologies Targeted sequencing (TS), Whole exome sequencing (WES), Whole genome sequencing (WGS), and the use of gene panels or gene lists for clinical diagnostic purposes. These methods primarily assess nucleotide sequence but can also detect copy number variants and many tandem repeat expansions, greatly simplifying diagnostic algorithms for movement disorders. Studies evaluating the efficacy of NGS in diagnosing movement disorders have reported a diagnostic yield of up... (More)

New generation sequencing (NGS) genetic testing is a powerful diagnostic tool and is increasingly used in the clinical workup of patients, especially in unusual presentations or where a positive family history suggests heritable disease. This review addresses the NGS technologies Targeted sequencing (TS), Whole exome sequencing (WES), Whole genome sequencing (WGS), and the use of gene panels or gene lists for clinical diagnostic purposes. These methods primarily assess nucleotide sequence but can also detect copy number variants and many tandem repeat expansions, greatly simplifying diagnostic algorithms for movement disorders. Studies evaluating the efficacy of NGS in diagnosing movement disorders have reported a diagnostic yield of up to 10.1% for familial and 15.7% for early-onset PD, 11.7–37.5% for dystonia, 12.1–61.8% for ataxia/spastic paraplegia and 11.3–28% for combined movement disorders. Patient selection and stringency in the interpretation of the detected variants and genotypes affect diagnostic yield. Careful comparison of the patient's or family's disease features with the previously reported phenotype associated with the same variant or gene can avoid false-positive diagnoses, although some genes are implicated in various phenotypes. Moving from TS to WES and WGS increases the number of patients correctly diagnosed, but for many patients, a genetic cause cannot be identified today. However, new genetically defined entities are discovered at rapid pace, and genetic databases and our knowledge of genotype-phenotype correlations expand steadily. We discuss the need for clear communication of genetic results and suggest a list of aspects to consider when reporting neurogenetic disorders using NGS testing.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Ataxia, Dystonia, Genetics, Movement disorders, New generation sequencing, Parkinson disease
in
Parkinsonism and Related Disorders
volume
73
pages
13 pages
publisher
Elsevier
external identifiers
  • scopus:85082772802
  • pmid:32273229
ISSN
1353-8020
DOI
10.1016/j.parkreldis.2020.02.015
language
English
LU publication?
yes
id
d2bcffe8-4d59-4e3b-b48c-cc73645b4ce6
date added to LUP
2020-04-24 14:41:22
date last changed
2021-06-20 06:10:44
@article{d2bcffe8-4d59-4e3b-b48c-cc73645b4ce6,
  abstract     = {<p>New generation sequencing (NGS) genetic testing is a powerful diagnostic tool and is increasingly used in the clinical workup of patients, especially in unusual presentations or where a positive family history suggests heritable disease. This review addresses the NGS technologies Targeted sequencing (TS), Whole exome sequencing (WES), Whole genome sequencing (WGS), and the use of gene panels or gene lists for clinical diagnostic purposes. These methods primarily assess nucleotide sequence but can also detect copy number variants and many tandem repeat expansions, greatly simplifying diagnostic algorithms for movement disorders. Studies evaluating the efficacy of NGS in diagnosing movement disorders have reported a diagnostic yield of up to 10.1% for familial and 15.7% for early-onset PD, 11.7–37.5% for dystonia, 12.1–61.8% for ataxia/spastic paraplegia and 11.3–28% for combined movement disorders. Patient selection and stringency in the interpretation of the detected variants and genotypes affect diagnostic yield. Careful comparison of the patient's or family's disease features with the previously reported phenotype associated with the same variant or gene can avoid false-positive diagnoses, although some genes are implicated in various phenotypes. Moving from TS to WES and WGS increases the number of patients correctly diagnosed, but for many patients, a genetic cause cannot be identified today. However, new genetically defined entities are discovered at rapid pace, and genetic databases and our knowledge of genotype-phenotype correlations expand steadily. We discuss the need for clear communication of genetic results and suggest a list of aspects to consider when reporting neurogenetic disorders using NGS testing.</p>},
  author       = {Gorcenco, Sorina and Ilinca, Andreea and Almasoudi, Wejdan and Kafantari, Efthymia and Lindgren, Arne G. and Puschmann, Andreas},
  issn         = {1353-8020},
  language     = {eng},
  month        = {04},
  pages        = {72--84},
  publisher    = {Elsevier},
  series       = {Parkinsonism and Related Disorders},
  title        = {New generation genetic testing entering the clinic},
  url          = {http://dx.doi.org/10.1016/j.parkreldis.2020.02.015},
  doi          = {10.1016/j.parkreldis.2020.02.015},
  volume       = {73},
  year         = {2020},
}