Heterozygous RNF13 Truncating Variants Are Associated With Developmental and Epileptic Encephalopathy

Authors

• Donald R. Latner, HudsonAlpha Institute for Biotechnology, Huntsville, AL
• Susan M. Hiatt, HudsonAlpha Institute for Biotechnology, Huntsville, AL
• Candice R. Finnila, HudsonAlpha Institute for Biotechnology, Huntsville, AL
• Whitley V. Kelley, HudsonAlpha Institute for Biotechnology, Huntsville, AL
• Marla Johnston, LSU Health Sciences Center - New OrleansFollow
• Jessica Patrick-Esteve, LSU Health Sciences Center - New OrleansFollow
• Nour Elkhateeb, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
• Mona A. Kamel, Kasr Al-Ainy School of Medicine, Cairo, Egypt
• Tahsin Stefan Barakat, Erasmus MC University Medical Center, Rotterdam, the Netherlands
• Marjon van Slegtenhorst, Erasmus MC University Medical Center, Rotterdam, the Netherlands
• Martin A. Mensah, Max Planck Institute for Molecular Genetics, Berlin, Germany
• Lewis Pang, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
• Pamela Bowman, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
• Henrietta Lefroy, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
• Ruth Cleaver, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
• Rachel Palmquist, University of Utah, Salt Lake City, UT
• Amanda G.Sandoval Karamian, University of Utah School of Medicine, Salt Lake City, UT
• Emma E. Smith, Ambry Genetics, Aliso Viejo, CA
• Suha Bachir, Stanford University, Stanford, CA
• Kristin G. Monaghan, GeneDX LLC, Gaithersburg, MD
• Ingrid M. Wentzensen, GeneDX LLC, Gaithersburg, MD
• Cathy A. Stevens, University of Tennessee Health Science Center, Chattanooga, TN
• Jill Pouncey, Erlanger Health, Chattanooga, TN
• Elizabeth Fieg, Brigham and Women's Hospital, Boston, MA
• Joel B. Krier, Brigham and Women's Hospital, Boston, MA
• Claudio Melo de Gusmao, Mass General Brigham, Boston, MA
• J. Carl Pallais, Brigham and Women's Hospital, Boston, MA
• Peter T. Skidmore, Phoenix Children's Hospital, Phoenix, AZ
• et al

Document Type

Article

Publication Date

7-15-2026

Publication Title

American Journal of Medical Genetics Part A

Abstract

Developmental and epileptic encephalopathy 73 (DEE73; OMIM 618379) is an autosomal dominant severe neurodevelopmental disorder associated with pathogenic variants in the RING finger protein 13 gene (RNF13; OMIM 609247), which encodes a transmembrane E3 ubiquitin ligase. The phenotype of affected individuals includes microcephaly, seizures, intellectual disability, developmental delay, absent or limited speech, restricted movement, cortical blindness, and skeletal defects (hip dysplasia, club feet, scoliosis). The currently known DEE73 phenotype is based on two reports of four unrelated individuals: three with missense variants in a di-leucine motif that is essential for binding to the Adaptor Protein Complex 3 (AP-3), and one with a truncating variant located in the last exon. This case series of an additional 13 affected individuals with RNF13 variants (2 missense, 11 truncating) supports and broadens previous reports. Importantly, it helps to define a narrow but critical region of the protein that is intolerant to truncating variation, although the gene is not highly constrained.

PubMed ID

42458923

Comments

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Rights

© 2026 Wiley Periodicals LLC.

Recommended Citation

Latner, Donald R.; Hiatt, Susan M.; Finnila, Candice R.; Kelley, Whitley V.; Johnston, Marla; Patrick-Esteve, Jessica; Elkhateeb, Nour; Kamel, Mona A.; Barakat, Tahsin Stefan; van Slegtenhorst, Marjon; Mensah, Martin A.; Pang, Lewis; Bowman, Pamela; Lefroy, Henrietta; Cleaver, Ruth; Palmquist, Rachel; Karamian, Amanda G.Sandoval; Smith, Emma E.; Bachir, Suha; Monaghan, Kristin G.; Wentzensen, Ingrid M.; Stevens, Cathy A.; Pouncey, Jill; Fieg, Elizabeth; Krier, Joel B.; de Gusmao, Claudio Melo; Pallais, J. Carl; Skidmore, Peter T.; and al, et, "Heterozygous RNF13 Truncating Variants Are Associated With Developmental and Epileptic Encephalopathy" (2026). School of Medicine Faculty Publications. 4907.
https://digitalscholar.lsuhsc.edu/som_facpubs/4907
10.1002/ajmg.a.70241