JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome.
JARID2
developmental delay
intellectual disability
neurodevelopment
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
11
06
2020
accepted:
23
09
2020
revised:
15
09
2020
pubmed:
21
10
2020
medline:
4
6
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
JARID2, located on chromosome 6p22.3, is a regulator of histone methyltransferase complexes that is expressed in human neurons. So far, 13 individuals sharing clinical features including intellectual disability (ID) were reported with de novo heterozygous deletions in 6p22-p24 encompassing the full length JARID2 gene (OMIM 601594). However, all published individuals to date have a deletion of at least one other adjoining gene, making it difficult to determine if JARID2 is the critical gene responsible for the shared features. We aim to confirm JARID2 as a human disease gene and further elucidate the associated clinical phenotype. Chromosome microarray analysis, exome sequencing, and an online matching platform (GeneMatcher) were used to identify individuals with single-nucleotide variants or deletions involving JARID2. We report 16 individuals in 15 families with a deletion or single-nucleotide variant in JARID2. Several of these variants are likely to result in haploinsufficiency due to nonsense-mediated messenger RNA (mRNA) decay. All individuals have developmental delay and/or ID and share some overlapping clinical characteristics such as facial features with those who have larger deletions involving JARID2. We report that JARID2 haploinsufficiency leads to a clinically distinct neurodevelopmental syndrome, thus establishing gene-disease validity for the purpose of diagnostic reporting.
Identifiants
pubmed: 33077894
doi: 10.1038/s41436-020-00992-z
pii: S1098-3600(21)02552-1
doi:
Substances chimiques
JARID2 protein, human
0
Polycomb Repressive Complex 2
EC 2.1.1.43
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
374-383Subventions
Organisme : CIHR
Pays : Canada
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