Delineation of a novel neurodevelopmental syndrome associated with PAX5 haploinsufficiency.
PAX5
autism spectrum disorder
developmental delay
intellectual disability
seizures
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
22
11
2021
received:
25
08
2021
accepted:
12
01
2022
pubmed:
31
1
2022
medline:
5
4
2022
entrez:
30
1
2022
Statut:
ppublish
Résumé
PAX5 is a transcription factor associated with abnormal posterior midbrain and cerebellum development in mice. PAX5 is highly loss-of-function intolerant and missense constrained, and has been identified as a candidate gene for autism spectrum disorder (ASD). We describe 16 individuals from 12 families who carry deletions involving PAX5 and surrounding genes, de novo frameshift variants that are likely to trigger nonsense-mediated mRNA decay, a rare stop-gain variant, or missense variants that affect conserved amino acid residues. Four of these individuals were published previously but without detailed clinical descriptions. All these individuals have been diagnosed with one or more neurodevelopmental phenotypes including delayed developmental milestones (DD), intellectual disability (ID), and/or ASD. Seizures were documented in four individuals. No recurrent patterns of brain magnetic resonance imaging (MRI) findings, structural birth defects, or dysmorphic features were observed. Our findings suggest that PAX5 haploinsufficiency causes a neurodevelopmental disorder whose cardinal features include DD, variable ID, and/or ASD.
Identifiants
pubmed: 35094443
doi: 10.1002/humu.24332
pmc: PMC8960338
mid: NIHMS1772796
doi:
Substances chimiques
PAX5 Transcription Factor
0
PAX5 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
461-470Subventions
Organisme : NHGRI NIH HHS
ID : UM1 HG008900
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009141
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101221
Pays : United States
Organisme : NICHD NIH HHS
ID : K23 HD102589
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG011755
Pays : United States
Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
Biochem Cell Biol. 2000;78(5):629-38
pubmed: 11103953
Genesis. 2013 Apr;51(4):234-45
pubmed: 23349049
Cell. 2017 Oct 19;171(3):710-722.e12
pubmed: 28965761
Nat Genet. 2021 Aug;53(8):1125-1134
pubmed: 34312540
Development. 2000 Sep;127(17):3703-13
pubmed: 10934015
Nature. 2007 Apr 12;446(7137):758-64
pubmed: 17344859
Cell. 2019 Jan 24;176(3):535-548.e24
pubmed: 30661751
Nat Genet. 2017 Apr;49(4):515-526
pubmed: 28191889
Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10164-9
pubmed: 17553960
Nat Neurosci. 2017 Apr;20(4):602-611
pubmed: 28263302
Nat Genet. 2020 Jan;52(1):35-39
pubmed: 31873297
Hum Mutat. 2015 Oct;36(10):928-30
pubmed: 26220891
Nat Genet. 2018 May;50(5):727-736
pubmed: 29700473
Nat Commun. 2014 Nov 24;5:5595
pubmed: 25418537
Genes Dev. 1992 Sep;6(9):1589-607
pubmed: 1516825
Mech Dev. 1999 Apr;82(1-2):29-39
pubmed: 10354469
Nat Genet. 2013 Oct;45(10):1226-1231
pubmed: 24013638
Blood. 2019 Jan 17;133(3):280-284
pubmed: 30510083
Audiology. 1996 Jan-Feb;35(1):55-61
pubmed: 8790871
NPJ Genom Med. 2019 Aug 23;4:19
pubmed: 31452935
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
Nat Genet. 2019 Feb;51(2):296-307
pubmed: 30643249
Nat Genet. 2014 Mar;46(3):310-5
pubmed: 24487276
Cell. 1994 Dec 2;79(5):901-12
pubmed: 8001127
Neuron. 2012 Apr 26;74(2):285-99
pubmed: 22542183
Genome Med. 2021 Feb 22;13(1):31
pubmed: 33618777
Cell. 2020 Feb 6;180(3):568-584.e23
pubmed: 31981491