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Pitt-Hopkins Syndrome: Pathogenic and Likely Pathogenic Genetic Variants in Healthy Carriers
https://doi.org/10.25557/2073-7998.2025.09.103-106
Abstract
Pitt-Hopkins syndrome is a rare autosomal dominant disorder characterized by multiple pathological manifestations, including intellectual disability, speech impairment, significant cognitive and motor developmental delays, and distinctive facial dysmorphisms. The condition is caused by alterations in the nucleotide sequence of the TCF4 gene, which encodes a transcription factor critical for nervous system development and function. Although the spectrum of pathogenic variants in TCF4 has been well characterized, their asymptomatic carriage remains poorly documented in the literature. In this study, using the ClinVar and gnomAD databases, we identified seven pathogenic or likely pathogenic variants in healthy individuals: rs1568303086, rs751190049, rs121909121, rs863224934, rs1230192802, rs895426748, and rs1603624808. These findings highlight the need for functional analysis and potential reclassification of the rs1230192802 variant. The observed cases underscore the variable expressivity of TCF4 variants.
Supporting agencies: The study was supported by the Russian Science Foundation (project No. 23-75-01138).
About the Authors
R. R. Savchenko
Sirius University of Science and Technology
Russian Federation
Russian Federation
1, Olympic Ave., Sirius Federal Territory, Krasnodar region,354340
E. S. Socruto
Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics
Russian Federation
Russian Federation
10, Naberejnaya Ushaiki, Tomsk, 634050
V. E. Shavrak
Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics
Russian Federation
Russian Federation
10, Naberejnaya Ushaiki, Tomsk, 634050
E. V. Kondakova
Sirius University of Science and Technology; Lobachevsky State University of Nizhny Novgorod
Russian Federation
Russian Federation
1, Olympic Ave., Sirius Federal Territory, Krasnodar region,354340; 23, Prospekt Gagarina, Nizhny Novgorod, 603022
N. A. Skryabin
Tomsk National Research Medical Center of the Russian Academy of Sciences, Research Institute of Medical Genetics
Russian Federation
Russian Federation
10, Naberejnaya Ushaiki, Tomsk, 634050
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Review
For citations:
Savchenko R.R., Socruto E.S., Shavrak V.E., Kondakova E.V., Skryabin N.A. Pitt-Hopkins Syndrome: Pathogenic and Likely Pathogenic Genetic Variants in Healthy Carriers. Medical Genetics. 2025;24(9):103-106. (In Russ.) https://doi.org/10.25557/2073-7998.2025.09.103-106
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