Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature
Abstract Autosomal dominant CDK13-related disease is characterized by congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD). Heterozygous pathogenic variants, particularly missense variants in the kinase domain, have previously been described as dise...
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BMC
2025-01-01
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| Series: | Clinical Epigenetics |
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| Online Access: | https://doi.org/10.1186/s13148-024-01807-7 |
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| author | Jan Fischer Mariëlle Alders Marcel M. A. M. Mannens David Genevieve Karl Hackmann Evelin Schröck Bekim Sadikovic Joseph Porrmann |
| author_facet | Jan Fischer Mariëlle Alders Marcel M. A. M. Mannens David Genevieve Karl Hackmann Evelin Schröck Bekim Sadikovic Joseph Porrmann |
| author_sort | Jan Fischer |
| collection | DOAJ |
| description | Abstract Autosomal dominant CDK13-related disease is characterized by congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD). Heterozygous pathogenic variants, particularly missense variants in the kinase domain, have previously been described as disease causing. Using the determination of a methylation pattern and comparison with an established episignature, we reveal the first hypomorphic variant in the kinase domain of CDK13, leading to a never before described autosomal recessive form of CHDFIDD in a boy with characteristic features. This highlights the utility of episignatures in variant interpretation, as well as a potential novel diagnostic approach in unsolved cases or for disease prognosis. |
| format | Article |
| id | doaj-art-a5fedb9c64cf4918b4a228501c828bec |
| institution | Kabale University |
| issn | 1868-7083 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj-art-a5fedb9c64cf4918b4a228501c828bec2025-01-19T12:27:52ZengBMCClinical Epigenetics1868-70832025-01-011711610.1186/s13148-024-01807-7Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignatureJan Fischer0Mariëlle Alders1Marcel M. A. M. Mannens2David Genevieve3Karl Hackmann4Evelin Schröck5Bekim Sadikovic6Joseph Porrmann7Faculty of Medicine of TUD Dresden University of Technology, Institute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of TechnologyDepartment of Human Genetics, Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, University of AmsterdamDepartment of Human Genetics, Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, University of AmsterdamGenetic Department, Reference Center for Abnormal Development and Malformative Syndrome, Montpellier University, ERN ITHACA, CHU MontpellierFaculty of Medicine of TUD Dresden University of Technology, Institute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of TechnologyFaculty of Medicine of TUD Dresden University of Technology, Institute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of TechnologyVerspeeten Clinical Genome Centre, London Health Sciences CentreFaculty of Medicine of TUD Dresden University of Technology, Institute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of TechnologyAbstract Autosomal dominant CDK13-related disease is characterized by congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD). Heterozygous pathogenic variants, particularly missense variants in the kinase domain, have previously been described as disease causing. Using the determination of a methylation pattern and comparison with an established episignature, we reveal the first hypomorphic variant in the kinase domain of CDK13, leading to a never before described autosomal recessive form of CHDFIDD in a boy with characteristic features. This highlights the utility of episignatures in variant interpretation, as well as a potential novel diagnostic approach in unsolved cases or for disease prognosis.https://doi.org/10.1186/s13148-024-01807-7CDK13CHDFIDDDevelopmental delayEpisignature |
| spellingShingle | Jan Fischer Mariëlle Alders Marcel M. A. M. Mannens David Genevieve Karl Hackmann Evelin Schröck Bekim Sadikovic Joseph Porrmann Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature Clinical Epigenetics CDK13 CHDFIDD Developmental delay Episignature |
| title | Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature |
| title_full | Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature |
| title_fullStr | Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature |
| title_full_unstemmed | Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature |
| title_short | Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature |
| title_sort | validation of a hypomorphic variant in cdk13 as the cause of chdfidd with autosomal recessive inheritance through determination of an episignature |
| topic | CDK13 CHDFIDD Developmental delay Episignature |
| url | https://doi.org/10.1186/s13148-024-01807-7 |
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