Semantic Similarity Analysis Reveals Robust Gene-Disease Relationships in Developmental and Epileptic Encephalopathies.
Child, Preschool
Cohort Studies
Female
GABA Plasma Membrane Transport Proteins
/ genetics
Gene Expression
Gene Ontology
Humans
Male
Munc18 Proteins
/ genetics
Mutation
NAV1.1 Voltage-Gated Sodium Channel
/ genetics
Phenotype
Seizures
/ classification
Semantics
Shab Potassium Channels
/ genetics
Spasms, Infantile
/ classification
Speech Disorders
/ classification
Terminology as Topic
Exome Sequencing
Human Phenotype Ontology
childhood epilepsies
computational phenotypes
developmental and epileptic encephalopathies
electronic medical records
neurogenetic disorders
whole-exome sequencing
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
16
03
2020
accepted:
31
07
2020
pubmed:
28
8
2020
medline:
1
12
2020
entrez:
28
8
2020
Statut:
ppublish
Résumé
More than 100 genetic etiologies have been identified in developmental and epileptic encephalopathies (DEEs), but correlating genetic findings with clinical features at scale has remained a hurdle because of a lack of frameworks for analyzing heterogenous clinical data. Here, we analyzed 31,742 Human Phenotype Ontology (HPO) terms in 846 individuals with existing whole-exome trio data and assessed associated clinical features and phenotypic relatedness by using HPO-based semantic similarity analysis for individuals with de novo variants in the same gene. Gene-specific phenotypic signatures included associations of SCN1A with "complex febrile seizures" (HP: 0011172; p = 2.1 × 10
Identifiants
pubmed: 32853554
pii: S0002-9297(20)30271-8
doi: 10.1016/j.ajhg.2020.08.003
pmc: PMC7536581
pii:
doi:
Substances chimiques
GABA Plasma Membrane Transport Proteins
0
KCNB1 protein, human
0
Munc18 Proteins
0
NAV1.1 Voltage-Gated Sodium Channel
0
SCN1A protein, human
0
SLC6A1 protein, human
0
STXBP1 protein, human
0
Shab Potassium Channels
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
683-697Subventions
Organisme : NINDS NIH HHS
ID : U54 NS108874
Pays : United States
Organisme : NINDS NIH HHS
ID : K02 NS112600
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001878
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD105354
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS091008
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : U54 HD086984
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD090255
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
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