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Two faces of DNMT3A-associated pathology
https://doi.org/10.25557/2073-7998.2025.08.134-136
Abstract
The syndromic disorders of neuropsychiatric development associated with DNMT3A mutations have been described relatively recently. Interestingly, two dissimilar phenotypes are associated with DNMT3A defects: Tatton-Brown-Rahman syndrome (with macrocephaly and tall stature) and an extremely rare Hein-Sproul-Jackson syndrome (with microcephaly and short stature). We have identified two patients corresponding to the clinical signs of these syndromes. Whole-exome sequencing revealed rare variants of the DNMT3A gene. Patient with Hein-Sproul-Jackson syndrome demonstrated previously undescribed clinical features.
Keywords
developmental delay,
DNMT3A,
de novo mutations,
Hein-Sproul-Jackson syndrome,
Tatton-Brown-Rahman syndrome
Supporting agencies: The research was supported by the Russian Science Foundation grant 24-45-00067
About the Authors
O. S. Sharonova
Saint Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
194100; 2, Litovskaya st.; Saint Petersburg
K. E. Valyakina
Saint Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
194100; 2, Litovskaya st.; Saint Petersburg
P. R. Korzun
Saint Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
194100; 2, Litovskaya st.; Saint Petersburg
K. S. Malysheva
Saint Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
194100; 2, Litovskaya st.; Saint Petersburg
S. A. Laptiev
Saint Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
194100; 2, Litovskaya st.; Saint Petersburg
E. N. Suspitsin
Saint Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
194100; 2, Litovskaya st.; Saint Petersburg
References
1. Heyn P., Logan C.V., Fluteau A., et al. Gain-of-function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions. Nat Genet. 2019;51(1):96-105.
2. Tatton-Brown K., Zachariou A., Loveday C., et al. The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants. Wellcome Open Res. 2018;3:46.
3. Kim G.H., Kim J., Lee J., Jang D.H. A novel pathogenic variant of DNMT3A associated with craniosynostosis: a case report of Heyn-Sproul-Jackson syndrome. Front Pediatr. 2023;11:1165638.
4. Shen W., Heeley J.M., Carlston C.M., et al. The spectrum of DNMT3A variants in Tatton-Brown-Rahman syndrome overlaps with that in hematologic malignancies. Am J Med Genet A. 2017;173(11):3022-3028.
Review
For citations:
Sharonova O.S., Valyakina K.E., Korzun P.R., Malysheva K.S., Laptiev S.A., Suspitsin E.N. Two faces of DNMT3A-associated pathology. Medical Genetics. 2025;24(8):134-136. (In Russ.) https://doi.org/10.25557/2073-7998.2025.08.134-136
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