Exome sequencing in paediatric patients with movement disorders.
Genetic diagnosis
Movement disorders
Treatment
Whole exome sequencing
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
15 01 2021
15 01 2021
Historique:
received:
27
10
2020
accepted:
06
01
2021
entrez:
15
1
2021
pubmed:
16
1
2021
medline:
22
6
2021
Statut:
epublish
Résumé
Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis. We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation. A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.
Sections du résumé
BACKGROUND
Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis.
RESULTS
We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation.
CONCLUSIONS
A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.
Identifiants
pubmed: 33446253
doi: 10.1186/s13023-021-01688-6
pii: 10.1186/s13023-021-01688-6
pmc: PMC7809769
doi:
Substances chimiques
ATP1A3 protein, human
0
GNAO1 protein, human
0
Proteins
0
SPG11 protein, human
0
Spastin
EC 3.6.4.3
GTP-Binding Protein alpha Subunits, Gi-Go
EC 3.6.5.1
SPAST protein, human
EC 5.6.1.1
Sodium-Potassium-Exchanging ATPase
EC 7.2.2.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
32Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
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