Recurrent carotid paragangliomas in a syndromic patient with a heterozygous missense variant in DNA Methyltransferase 3 Alpha.
DNMT3A
exome sequencing
hypermethylation
paraganglioma
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:
21 Aug 2024
21 Aug 2024
Historique:
revised:
23
07
2024
received:
14
07
2023
accepted:
05
08
2024
medline:
21
8
2024
pubmed:
21
8
2024
entrez:
21
8
2024
Statut:
aheadofprint
Résumé
We report a 40-year-old African American female with a novel variant in exon 8 of DNA methyltransferase 3 alpha (DNMT3A), (NM_022552.4: c.905G>C, p.G302A) who presented with a history of recurrent carotid paragangliomas, mediastinal mass, intellectual disability, dysarthria, cholelithiasis, diabetes mellitus, hypertension, and dysmorphic features. We interpret this novel variant as likely pathogenic and causative for the patient's syndromic features of Heyn-Sproul-Jackson syndrome. Heyn-Sproul-Jackson syndrome is a condition caused by gain-of-function genetic changes in DNMT3A. Paragangliomas have also been observed in non-syndromic patients with genetic alterations in DNMT3A. We describe a patient with clinical features of Heyn-Sproul-Jackson syndrome such as intellectual disability, dysarthria, brachydactyly, and lack of brain MRI findings to add evidence to associate paragangliomas with DNMT3A and draw particular attention to the potential involvement of the proline-tryptophan-tryptophan-proline domain of DNMT3A.
Identifiants
pubmed: 39166703
doi: 10.1002/ajmg.a.63849
doi:
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e63849Subventions
Organisme : NHGRI NIH HHS
ID : R01HG011795
Pays : United States
Organisme : Jan and Dan Neurological Research Institute
Informations de copyright
© 2024 Wiley Periodicals LLC.
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