Biallelic PAN2 variants in individuals with a syndromic neurodevelopmental disorder and multiple congenital anomalies.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
17
09
2021
accepted:
17
02
2022
revised:
10
01
2022
pubmed:
20
3
2022
medline:
14
5
2022
entrez:
19
3
2022
Statut:
ppublish
Résumé
PAN2 encodes a subunit of a deadenylation complex with important functions in mRNA stability and post-transcriptional regulation of gene expression. A homozygous frameshift deletion in PAN2 was reported in a single affected individual with developmental delay and multiple congenital anomalies. Here, we describe five additional individuals from three unrelated families with homozygous predicted loss-of-function variants in PAN2. The affected individuals presented with significant overlap in their clinical features, including mild-moderate intellectual disability, hypotonia, sensorineural hearing loss, EEG abnormalities, congenital heart defects (tetralogy of Fallot, septal defects, dilated aortic root), urinary tract malformations, ophthalmological anomalies, short stature with other skeletal anomalies, and craniofacial features including flat occiput, ptosis, long philtrum, and short neck. Our data confirm that biallelic predicted loss-of-function variants in PAN2 cause a syndrome with multiple congenital anomalies, and suggest an important role of mRNA polyA tail length for proper organ formation.
Identifiants
pubmed: 35304602
doi: 10.1038/s41431-022-01077-y
pii: 10.1038/s41431-022-01077-y
pmc: PMC9090724
doi:
Substances chimiques
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
611-618Subventions
Organisme : CIHR
Pays : Canada
Informations de copyright
© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.
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