Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2023 Sep;11(9):e2192.
doi: 10.1002/mgg3.2192. Epub 2023 May 10.

Novel heterozygous variants in the EP300 gene cause Rubinstein-Taybi syndrome 2: Reports from two Chinese children

Caiqi Du  1 , Zhuoguang Li  1   2 , Biao Zou  1 , Xuesong Li  1 , Fan Chen  1 , Yan Liang  1 , Xiaoping Luo  1 , Sainan Shu  1
Affiliations
Case Reports

Novel heterozygous variants in the EP300 gene cause Rubinstein-Taybi syndrome 2: Reports from two Chinese children

Caiqi Du et al. Mol Genet Genomic Med. 2023 Sep.

Abstract

Background: Rubinstein-Taybi syndrome (RSTS) is a rare autosomal-dominant genetic disease caused by variants of CREBBP (RSTS1) or EP300 (RSTS2) gene. RSTS2 is much less common, with less than 200 reported cases worldwide to date. More reports are still needed to increase the understanding of its clinical manifestations and genetic characteristics.

Methods: The clinical data of two children with RSTS2 were analyzed retrospectively, and their clinical manifestations, auxiliary examinations, and mutational spectrum were summarized. Liquid chromatography-tandem mass spectrometer (LC-MS/MS) technology was used to detect the levels of steroid hormones if possible.

Results: After analyzing the clinical and genetic characteristics of two boys with RSTS2 (0.7 and 10.4 years old, respectively) admitted in our hospital, we identified two novel heterozygous variants in the EP300 exon 22 (c.3750C > A, p. Cys1250*, pathogenic; c.1889A > G, p. Tyr630Cys, likely pathogenic), which could account for their phenotype. In addition to common clinical manifestations such as special facial features, microcephaly, growth retardation, intellectual disability, speech delay, congenital heart defect, recurrent respiratory infections, and immunodeficiency, we found one of them had a rare feature of adrenal insufficiency, and LC-MS/MS detection showed an overall decrease in steroid hormones.

Conclusion: In our study, we identified two novel variants in the EP300 exon 22, and for the first time, we reported a case of RSTS2 associated with adrenal insufficiency, which will enrich the clinical and mutational spectrum of this syndrome.

Keywords: EP300; LC-MS/MS; Rubinstein-Taybi syndrome; adrenal insufficiency; genotype.

PubMed Disclaimer

Conflict of interest statement

All authors declare that they have no conflict of interest.

Figures

FIGURE 1
FIGURE 1
The trend of steroid hormone changes in patient 1 (LC–MS/MS technology, the arrow shows the trend of hormone changes).
FIGURE 2
FIGURE 2
The genetic test results of the two RSTS2 patients and their parents (Genome reference sequence: GRCh37/hg19). Patient 1: (a): a heterozygous variant of EP300 in the proband (c.3750C > A, p. Cys1250*). (b): no variant of EP300 in the proband's father. (c): no variant of EP300 in the proband's mother. Patient 2: (d): a heterozygous variant of EP300 in the proband (c.1889A > G, p. Tyr630Cys). (e): no variant of EP300 in the proband's father. (f): no variant of EP300 in the proband's mother.
See this image and copyright information in PMC

References

    1. Bamforth, S. D. , Bragança, J. , Eloranta, J. J. , Murdoch, J. N. , Marques, F. I. , Kranc, K. R. , Farza, H. , Henderson, D. J. , Hurst, H. C. , & Bhattacharya, S. (2001). Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co‐activator. Nature Genetics, 29(4), 469–474. 10.1038/ng768 - DOI - PubMed
    1. Chen, W. Y. , Juan, L. J. , & Chung, B. C. (2005). SF‐1 (nuclear receptor 5A1) activity is activated by cyclic AMP via p300‐mediated recruitment to active foci, acetylation, and increased DNA binding. Molecular and Cellular Biology, 25(23), 10442–10453. 10.1128/mcb.25.23.10442-10453.2005 - DOI - PMC - PubMed
    1. Dahl, S. R. , Nermoen, I. , Brønstad, I. , Husebye, E. S. , Løvås, K. , & Thorsby, P. M. (2018). Assay of steroids by liquid chromatography‐tandem mass spectrometry in monitoring 21‐hydroxylase deficiency. Endocrine Connections, 7(12), 1542–1550. 10.1530/ec-18-0453 - DOI - PMC - PubMed
    1. Kasper, L. H. , Fukuyama, T. , Lerach, S. , Chang, Y. , Xu, W. , Wu, S. , Boyd, K. L. , & Brindle, P. K. (2013). Genetic interaction between mutations in c‐Myb and the KIX domains of CBP and p300 affects multiple blood cell lineages and influences both gene activation and repression. PLoS ONE, 8(12), e82684. 10.1371/journal.pone.0082684 - DOI - PMC - PubMed
    1. Korzus, E. (2017). Rubinstein–Taybi syndrome and epigenetic alterations. Advances in Experimental Medicine and Biology, 978, 39–62. 10.1007/978-3-319-53889-1_3 - DOI - PMC - PubMed

Publication types

LinkOut - more resources