Whole-exome sequencing and adrenocorticotropic hormone therapy in individuals with infantile spasms.
Journal
Developmental medicine and child neurology
ISSN: 1469-8749
Titre abrégé: Dev Med Child Neurol
Pays: England
ID NLM: 0006761
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
22
10
2021
received:
18
04
2021
accepted:
25
10
2021
entrez:
13
7
2022
pubmed:
14
7
2022
medline:
16
7
2022
Statut:
ppublish
Résumé
To identify additional genes associated with infantile spasms using a cohort with defined infantile spasms. Whole-exome sequencing (WES) was performed on 21 consented individuals with infantile spasms and their unaffected parents (a trio-based study). Clinical history and imaging were reviewed. Potentially deleterious exonic variants were identified and segregated. To refine potential candidates, variants were further prioritized on the basis of evidence for relevance to disease phenotype or known associations with infantile spasms, epilepsy, or neurological disease. Likely pathogenic de novo variants were identified in NR2F1, GNB1, NEUROD2, GABRA2, and NDUFAF5. Suggestive dominant and recessive candidate variants were identified in PEMT, DYNC1I1, ASXL1, RALGAPB, and STRADA; further confirmation is required to support their relevance to disease etiology. This study supports the utility of WES in uncovering the genetic etiology in undiagnosed individuals with infantile spasms with an overall yield of five out of 21. High-priority candidates were identified in an additional five individuals. WES provides additional support for previously described disease-associated genes and expands their already broad mutational and phenotypic spectrum.
Substances chimiques
Adrenocorticotropic Hormone
9002-60-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
633-640Subventions
Organisme : NINDS NIH HHS
ID : R00NS089858
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR001423
Pays : United States
Investigateurs
Elizabeth A Geiger
(EA)
Jonathan Gunti
(J)
Gina Vanderveen
(G)
Informations de copyright
© 2021 Mac Keith Press.
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