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DPF2-related Coffin-Siris syndrome type 7 in two generations


Kolokotronis, Konstantinos; Suter, Aude-Annick; Ivanovski, Ivan; Frey, Tanja; Bahr, Angela; Rauch, Anita; Steindl, Katharina (2024). DPF2-related Coffin-Siris syndrome type 7 in two generations. European Journal of Medical Genetics, 69:104945.

Abstract

To date 11 patients with Coffin-Siris syndrome type 7 (OMIM 618027) have been described since the first literature report. All reported patients carried de novo variants with presumed dominant negative effect, which localized in the PHD1/PHD2 domains of DPF2.

Here we report on the first familial case of Coffin-Siris syndrome type 7. The index patient presented at the age of 1 year with failure to thrive and ectodermal anomalies. The genetic analysis using whole exome sequencing showed a likely pathogenic missense variant in the PHD1 region. The family analysis showed that the mother as well as the older brother of the index patient also carried the detected DPF2 variant in heterozygous state. The mother had a history of school difficulties but no history of failure to thrive and was overall milder affected. The brother showed developmental delay with autistic features, ectodermal anomalies and overlapping morphologic features but did not have a history of growth failure problems.

To our knowledge this is the first report of an inherited variant in DPF2, underlining the variability of the associated phenotype as well as the importance of considering inherited DPF2 variants during the variant filtering strategy of whole exome data.

Abstract

To date 11 patients with Coffin-Siris syndrome type 7 (OMIM 618027) have been described since the first literature report. All reported patients carried de novo variants with presumed dominant negative effect, which localized in the PHD1/PHD2 domains of DPF2.

Here we report on the first familial case of Coffin-Siris syndrome type 7. The index patient presented at the age of 1 year with failure to thrive and ectodermal anomalies. The genetic analysis using whole exome sequencing showed a likely pathogenic missense variant in the PHD1 region. The family analysis showed that the mother as well as the older brother of the index patient also carried the detected DPF2 variant in heterozygous state. The mother had a history of school difficulties but no history of failure to thrive and was overall milder affected. The brother showed developmental delay with autistic features, ectodermal anomalies and overlapping morphologic features but did not have a history of growth failure problems.

To our knowledge this is the first report of an inherited variant in DPF2, underlining the variability of the associated phenotype as well as the importance of considering inherited DPF2 variants during the variant filtering strategy of whole exome data.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Institute of Medical Genetics
08 Research Priority Programs > Adaptive Brain Circuits in Development and Learning (AdaBD)
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:Genetics, Genetics (clinical), Coffin–Siris syndrome, maternally Inherited, de novo, dominant negative, DPF2-related Coffin-Siris syndrome type 7 in two generations
Language:English
Date:1 June 2024
Deposited On:06 May 2024 15:13
Last Modified:30 Jun 2024 01:41
Publisher:Elsevier
ISSN:1769-7212
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.ejmg.2024.104945
Related URLs:https://api.semanticscholar.org/CorpusID:269487510 (Library Catalogue)
PubMed ID:38697389
Other Identification Number:Corpus ID: 269487510
Project Information:
  • : FunderUniversity of Zurich (UZH)
  • : Grant IDURPP ITINERARE
  • : Project TitleUniversity Research Priority Program ITINERARE: Innovative Therapies in Rare Diseases, Zurich, Switzerland
  • : Project Websitehttps://www.itinerare.uzh.ch/en.html
  • : FunderUniversity of Zurich (UZH)
  • : Grant IDURPP AdaBD
  • : Project TitleUniversity Research Priority Program AdaBD: Adaptive Brain Circuits in Development and Learning, Zurich, Switzerland
  • : Project Websitehttps://www.adabd.uzh.ch/en.html