PPP2R1A neurodevelopmental disorder is associated with congenital heart defects.
PPP2R1A
congenital heart defects
neurodevelopmental disorder
protein phosphatase 2A
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
revised:
03
06
2022
received:
18
03
2022
accepted:
05
07
2022
entrez:
8
10
2022
pubmed:
9
10
2022
medline:
12
10
2022
Statut:
ppublish
Résumé
Protein phosphatase 2A (PP2A) is a heterotrimeric serine/threonine phosphatase that regulates numerous biological processes. PPP2R1A encodes the scaffolding "Aα" subunit of PP2A. To date, nearly 40 patients have been previously reported with 19 different pathogenic PPP2R1A variants, with phenotypes including intellectual disability, developmental delay, epilepsy, infant agenesis/dysgenesis of the corpus callosum, and dysmorphic features. Apart from a single case, severe congenital heart defects (CHD) have not been described. We report four new unrelated individuals with pathogenic heterozygous PPP2R1A variants and CHD and model the crystal structure of several variants to investigate mechanisms of phenotype disparity. Individuals 1 and 2 have a previously described variant (c.548G>A, p.R183Q) and similar phenotypes with severe ventriculomegaly, agenesis/dysgenesis of the corpus callosum, and severe CHD. Individual 3 also has a recurrent variant (c.544C>T, p.R182W) and presented with agenesis of corpus callosum, ventriculomegaly, mild pulmonic stenosis, and small patent foramen ovale. Individual 4 has a novel variant (c.536C>A, p.P179H), ventriculomegaly, and atrial septal defect. To conclude, we propose expansion of the phenotype of PPP2R1A neurodevelopmental disorder to include CHD. Further, the R183Q variant has now been described in three individuals, all with severe neurologic abnormalities, severe CHD, and early death suggesting that this variant may be particularly deleterious.
Identifiants
pubmed: 36209351
doi: 10.1002/ajmg.a.62946
doi:
Substances chimiques
PPP2R1A protein, human
0
Transcription Factors
0
Serine
452VLY9402
Protein Phosphatase 2
EC 3.1.3.16
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3262-3277Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
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