De Novo and Inherited Pathogenic Variants in KDM3B Cause Intellectual Disability, Short Stature, and Facial Dysmorphism
Publication year
2019Author(s)
Source
American Journal of Human Genetics, 104, 4, (2019), pp. 758-766ISSN
Publication type
Article / Letter to editor

Display more detailsDisplay less details
Organization
Human Genetics
Radboudumc Extern
CMBI
Journal title
American Journal of Human Genetics
Volume
vol. 104
Issue
iss. 4
Page start
p. 758
Page end
p. 766
Subject
Radboudumc 14: Tumours of the digestive tract RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 19: Nanomedicine RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 6: Metabolic Disorders RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience; Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health SciencesAbstract
By using exome sequencing and a gene matching approach, we identified de novo and inherited pathogenic variants in KDM3B in 14 unrelated individuals and three affected parents with varying degrees of intellectual disability (ID) or developmental delay (DD) and short stature. The individuals share additional phenotypic features that include feeding difficulties in infancy, joint hypermobility, and characteristic facial features such as a wide mouth, a pointed chin, long ears, and a low columella. Notably, two individuals developed cancer, acute myeloid leukemia and Hodgkin lymphoma, in childhood. KDM3B encodes for a histone demethylase and is involved in H3K9 demethylation, a crucial part of chromatin modification required for transcriptional regulation. We identified missense and truncating variants, suggesting that KDM3B haploinsufficiency is the underlying mechanism for this syndrome. By using a hybrid facial-recognition model, we show that individuals with a pathogenic variant in KDM3B have a facial gestalt, and that they show significant facial similarity compared to control individuals with ID. In conclusion, pathogenic variants in KDM3B cause a syndrome characterized by ID, short stature, and facial dysmorphism.
This item appears in the following Collection(s)
- Academic publications [204994]
- Electronic publications [103240]
- Faculty of Medical Sciences [81051]
- Open Access publications [71780]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.