Duncan NRI Faculty and Staff Publications
Language
English
Publication Date
1-1-2025
Journal
American Journal of Medical Genetics Part A
DOI
10.1002/ajmg.a.63849
PMID
39166703
PMCID
PMC11637962
PubMedCentral® Posted Date
1-1-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
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.
Keywords
Humans, Female, DNA Methyltransferase 3A, Adult, Mutation, Missense, DNA (Cytosine-5-)-Methyltransferases, Paraganglioma, Heterozygote, Syndrome, Phenotype, Intellectual Disability, DNMT3A, hypermethylation, paraganglioma, exome sequencing
Published Open-Access
yes
Recommended Citation
German, Ryan J; Vuocolo, Blake; Vossaert, Liesbeth; et al., "Recurrent Carotid Paragangliomas in a Syndromic Patient With a Heterozygous Missense Variant in DNA Methyltransferase 3 Alpha" (2025). Duncan NRI Faculty and Staff Publications. 227.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/227
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