Duplication/triplication mosaicism of EBF3 and expansion of the EBF3 neurodevelopmental disorder phenotype

Erika Ignatius; Riina Puosi; Maarit Palomäki; Noora Forsbom; Max Pohjanpelto; Tiina Alitalo; Anna-Kaisa Anttonen; Kristiina Avela; Leena Haataja; Christopher J Carroll; Tuula Lönnqvist; Pirjo Isohanni

doi:10.1016/j.ejpn.2021.12.012

Duplication/triplication mosaicism of EBF3 and expansion of the EBF3 neurodevelopmental disorder phenotype

Eur J Paediatr Neurol. 2022 Mar:37:1-7. doi: 10.1016/j.ejpn.2021.12.012. Epub 2021 Dec 26.

Authors

Affiliations

¹ Department of Child Neurology, Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Programs Unit, Stem Cells and Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
² Department of Child Neurology, Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
³ Department of Radiology, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁴ Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁵ Research Programs Unit, Stem Cells and Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁶ Laboratory of Genetics, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁷ Laboratory of Genetics, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Clinical Genetics, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁸ Department of Clinical Genetics, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁹ Genetics Research Centre, Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, United Kingdom.
¹⁰ Department of Child Neurology, Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Programs Unit, Stem Cells and Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Electronic address: [email protected].

PMID: 34999443
DOI: 10.1016/j.ejpn.2021.12.012

Abstract

Deleterious variants in the transcription factor early B-cell factor 3 (EBF3) are known to cause a neurodevelopmental disorder (EBF3-NDD). We report eleven individuals with EBF3 variants, including an individual with a duplication/triplication mosaicism of a region encompassing EBF3 and a phenotype consistent with EBF3-NDD, which may reflect the importance of EBF3 gene-dosage for neurodevelopment. The phenotype of individuals in this cohort was quite mild compared to the core phenotype of previously described individuals. Although ataxia tended to wane with age, we show that cognitive difficulties may increase, and we recommend that individuals with EBF3-NDD have systematic neuropsychological follow-up.

Keywords: 10q26; Ataxia; EBF3; EBF3-NDD; HADDS; Phenotype.

MeSH terms

Ataxia / genetics
Gene Dosage
Humans
Mosaicism*
Neurodevelopmental Disorders* / genetics
Phenotype
Transcription Factors* / genetics

Substances

EBF3 protein, human
Transcription Factors