Paralog Studies Augment Gene Discovery: DDX and DHX Genes.
DExD/H-box RNA helicase family
developmental delay
human paralogs
intellectual disability
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 08 2019
01 08 2019
Historique:
received:
10
12
2018
accepted:
31
05
2019
pubmed:
2
7
2019
medline:
17
3
2020
entrez:
2
7
2019
Statut:
ppublish
Résumé
Members of a paralogous gene family in which variation in one gene is known to cause disease are eight times more likely to also be associated with human disease. Recent studies have elucidated DHX30 and DDX3X as genes for which pathogenic variant alleles are involved in neurodevelopmental disorders. We hypothesized that variants in paralogous genes encoding members of the DExD/H-box RNA helicase superfamily might also underlie developmental delay and/or intellectual disability (DD and/or ID) disease phenotypes. Here we describe 15 unrelated individuals who have DD and/or ID, central nervous system (CNS) dysfunction, vertebral anomalies, and dysmorphic features and were found to have probably damaging variants in DExD/H-box RNA helicase genes. In addition, these individuals exhibit a variety of other tissue and organ system involvement including ocular, outer ear, hearing, cardiac, and kidney tissues. Five individuals with homozygous (one), compound-heterozygous (two), or de novo (two) missense variants in DHX37 were identified by exome sequencing. We identified ten total individuals with missense variants in three other DDX/DHX paralogs: DHX16 (four individuals), DDX54 (three individuals), and DHX34 (three individuals). Most identified variants are rare, predicted to be damaging, and occur at conserved amino acid residues. Taken together, these 15 individuals implicate the DExD/H-box helicases in both dominantly and recessively inherited neurodevelopmental phenotypes and highlight the potential for more than one disease mechanism underlying these disorders.
Identifiants
pubmed: 31256877
pii: S0002-9297(19)30226-5
doi: 10.1016/j.ajhg.2019.06.001
pmc: PMC6698803
pii:
doi:
Substances chimiques
Neoplasm Proteins
0
DDX54 protein, human
EC 2.7.7.-
DHX16 protein, human
EC 2.7.7.-
DHX34 protein, human
EC 2.7.7.-
DEAD-box RNA Helicases
EC 3.6.4.13
RNA Helicases
EC 3.6.4.13
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
302-316Subventions
Organisme : NHGRI NIH HHS
ID : UM1 HG006542
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS105078
Pays : United States
Organisme : NHGRI NIH HHS
ID : K08 HG008986
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK078121
Pays : United States
Organisme : NIDDK NIH HHS
ID : K12 DK083014
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006493
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008307
Pays : United States
Informations de copyright
Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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