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Whole exome sequencing of familial, combined or complex dystonia

Kafantari, E. LU and Puschmann, A. LU orcid (2023) In Parkinsonism & Related Disorders 113(Supp). p.65-66
Abstract
Background: To determine the usefulness of whole exome sequencing
(WES) in the diagnostic evaluation of patients and small families with
familial, combined and/or complex forms of dystonia identified from an
adult neurology clinic at a tertiary center, and to set up a computational
pathway for the bioinformatics analyses.
Methods: By mail, we contacted all 347 patients from our department who
during a 4-year period had an ICD-10 diagnosis of dystonia. Of these, 122
were re-examined within our research study. Patients who had combined
and/or complex dystonia phenotypes and patients who reported close
family members with dystonia were examined by WES. Different
computational approaches followed... (More)
Background: To determine the usefulness of whole exome sequencing
(WES) in the diagnostic evaluation of patients and small families with
familial, combined and/or complex forms of dystonia identified from an
adult neurology clinic at a tertiary center, and to set up a computational
pathway for the bioinformatics analyses.
Methods: By mail, we contacted all 347 patients from our department who
during a 4-year period had an ICD-10 diagnosis of dystonia. Of these, 122
were re-examined within our research study. Patients who had combined
and/or complex dystonia phenotypes and patients who reported close
family members with dystonia were examined by WES. Different
computational approaches followed (co-segregation or trio analysis,
filtering variants based on an in-house gene list with more than 500 dystonia nuclear and mitochondrial genes etc.). Copy number variants (CNVs)
were also detected by using in-silico tools.
Results: Re-examination revealed that 11 of 122 (9.0%) of patients had
other disorders. Of the remaining 111 patients, fourteen had familial, combined or complex dystonia phenotypes starting at mean 37.6 (SD 14.9)
years and were analysed by WES. For 5 of these, a definite or candidate
monogenic disease cause was identified (table).
The diagnostic yield in this project was 35,7% with positive or likely positive findings. Two of 5 patients had variants that had been described previously (40%) and the remaining 3 carried putatively pathogenic variants (60%).
Conclusions: Candidate disease-causing variants were identified in 5 out of 14 cases investigated, all these had combined or complex dystonia and relatively young onset (mean 22.3, SD 11.3 years). CNV analysis is relevant in the genetic workup of familial/combined/complex dystonia. (Less)
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author
and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Parkinsonism & Related Disorders
volume
113
issue
Supp
article number
P186
pages
65 - 66
publisher
Elsevier
ISSN
1353-8020
DOI
10.1016/j.parkreldis.2023.105722
language
English
LU publication?
yes
id
e437cb31-ebf5-4cd8-af2b-92b02ba36ba3
date added to LUP
2023-08-31 21:39:34
date last changed
2023-09-01 09:32:06
@misc{e437cb31-ebf5-4cd8-af2b-92b02ba36ba3,
  abstract     = {{Background: To determine the usefulness of whole exome sequencing<br/>(WES) in the diagnostic evaluation of patients and small families with<br/>familial, combined and/or complex forms of dystonia identified from an<br/>adult neurology clinic at a tertiary center, and to set up a computational<br/>pathway for the bioinformatics analyses.<br/>Methods: By mail, we contacted all 347 patients from our department who<br/>during a 4-year period had an ICD-10 diagnosis of dystonia. Of these, 122<br/>were re-examined within our research study. Patients who had combined<br/>and/or complex dystonia phenotypes and patients who reported close<br/>family members with dystonia were examined by WES. Different<br/>computational approaches followed (co-segregation or trio analysis,<br/>filtering variants based on an in-house gene list with more than 500 dystonia nuclear and mitochondrial genes etc.). Copy number variants (CNVs)<br/>were also detected by using in-silico tools.<br/>Results: Re-examination revealed that 11 of 122 (9.0%) of patients had<br/>other disorders. Of the remaining 111 patients, fourteen had familial, combined or complex dystonia phenotypes starting at mean 37.6 (SD 14.9)<br/>years and were analysed by WES. For 5 of these, a definite or candidate<br/>monogenic disease cause was identified (table).<br/>The diagnostic yield in this project was 35,7% with positive or likely positive findings. Two of 5 patients had variants that had been described previously (40%) and the remaining 3 carried putatively pathogenic variants (60%).<br/>Conclusions: Candidate disease-causing variants were identified in 5 out of 14 cases investigated, all these had combined or complex dystonia and relatively young onset (mean 22.3, SD 11.3 years). CNV analysis is relevant in the genetic workup of familial/combined/complex dystonia.}},
  author       = {{Kafantari, E. and Puschmann, A.}},
  issn         = {{1353-8020}},
  language     = {{eng}},
  note         = {{Conference Abstract}},
  number       = {{Supp}},
  pages        = {{65--66}},
  publisher    = {{Elsevier}},
  series       = {{Parkinsonism & Related Disorders}},
  title        = {{Whole exome sequencing of familial, combined or complex dystonia}},
  url          = {{http://dx.doi.org/10.1016/j.parkreldis.2023.105722}},
  doi          = {{10.1016/j.parkreldis.2023.105722}},
  volume       = {{113}},
  year         = {{2023}},
}