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
. 2022 Jul;188(7):2129-2134.
doi: 10.1002/ajmg.a.62719. Epub 2022 Mar 9.

Identical EP300 variant leading to Rubinstein-Taybi syndrome with different clinical and immunologic phenotype

Francesco Saettini  1   2 , Grazia Fazio  2 , Maria Teresa Bonati  3 , Daniele Moratto  4 , Valentina Massa  5 , Elisabetta Di Fede  5 , Silvia Castiglioni  5 , Daniela Marchetti  6 , Marco Chiarini  4 , Alessandra Sottini  7 , Maria Iascone  6 , Giovanni Cazzaniga  2 , Luisa Imberti  7 , Andrea Biondi  1   2 , Cristina Gervasini  5 , Raffaele Badolato  8
Affiliations
Free article
Case Reports

Identical EP300 variant leading to Rubinstein-Taybi syndrome with different clinical and immunologic phenotype

Francesco Saettini et al. Am J Med Genet A. 2022 Jul.
Free article

Abstract

The Rubinstein-Taybi syndrome (RSTS) is a rare developmental disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, intellectual disability, growth deficiency, and recurrent infections. Mutations in the cyclic adenosine monophosphate response element-binding protein (CREB)-binding protein (CREBBP) or in the E1A-associated protein p300 (EP300) genes have been demonstrated in 55% (RSTS1) and up to 8% of the patients (RSTS2), respectively. Dysfunction of immune response has been reported in a subgroup of individuals with RSTS. Here we characterize two patients carrying the same EP300 variant and distinctive RSTS features (including congenital heart abnormalities, short stature, feeding problems, and gastroesophageal reflux). Whole exome sequencing did not support a dual molecular diagnosis hypothesis. Nonetheless, patients showed distinct clinical manifestations and immunological features. The most severe phenotype was associated with reduced T-cell production and diversity. This latter feature was confirmed in a control group of four RSTS patients.

Keywords: CREBBP; EP300; Rubinstein-Taybi syndrome; inborn errors of immunity; syndromic immunodeficiency.

PubMed Disclaimer

References

REFERENCES

    1. Adams, S. P., Kricke, S., Ralph, E., Gilmour, N., & Gilmour, K. C. (2018). A comparison of TRECs and flow cytometry for naive T cell quantification. Clinical and Experimental Immunology, 191(2), 198-202. https://doi.org/10.1111/cei.13062
    1. Baldo, C., Casareto, L., Renieri, A., Merla, G., Garavaglia, B., Goldwurm, S., Pegoraro, E., Moggio, M., Mora, M., Politano, L., Sangiorgi, L., Mazzotti, R., Viotti, V., Meloni, I., Pellico, M. T., Barzaghi, C., Wang, C. M., Monaco, L., & Filocamo, M. (2016). The alliance between genetic biobanks and patient organisations: The experience of the telethon network of genetic biobanks. Orphanet Journal of Rare Diseases, 11(1), 142. https://doi.org/10.1186/s13023-016-0527-7
    1. Bousfiha, A., Jeddane, L., Picard, C., Al-Herz, W., Ailal, F., Chatila, T., Cunningham-Rundles, C., Etzioni, A., Franco, J. L., Holland, S. M., Klein, C., Morio, T., Ochs, H. D., Oksenhendler, E., Puck, J., Torgerson, T. R., Casanova, J. L., Sullivan, K. E., & Tangye, S. G. (2020). Human inborn errors of immunity: 2019 update of the IUIS phenotypical classification. Journal of Clinical Immunology, 40(1), 66-81. https://doi.org/10.1007/s10875-020-00758-x
    1. Corneo, B., Moshous, D., Güngör, T., Wulffraat, N., Philippet, P., Le Deist, F. L., Fischer, A., & de Villartay, J. P. (2001). Identical mutations in RAG1 or RAG2 genes leading to defective V(D)J recombinase activity can cause either T-B-severe combined immune deficiency or Omenn syndrome. Blood, 97(9), 2772-2776. https://doi.org/10.1182/blood.v97.9.2772
    1. Lopez-Atalaya, J. P., Gervasini, C., Mottadelli, F., Spena, S., Piccione, M., Scarano, G., Selicorni, A., Barco, A., & Larizza, L. (2012). Histone acetylation deficits in lymphoblastoid cell lines from patients with Rubinstein-Taybi syndrome. Journal of Medical Genetics, 49(1), 66-74. https://doi.org/10.1136/jmedgenet-2011-100354

Publication types