35 Individuals With HUWE1 ‐Related Neurodevelopmental Disorder and Suggested Clinical Evaluations
Year: 2026
Type: article
Study design: Observational Study
Abstract: HUWE1 (HECT, UBA, and WWE Domain Containing E3 Ubiquitin Protein Ligase1, OMIM 300697), located at Xp11.22, encodes a ubiquitin ligase that is highly conserved across species. Genetic variants in HUWE1 described in multiple independent studies cause X-linked intellectual disability, including in the patients identified by Juberg, Marsidi, and Brooks. This report describes 35 additional cases of individuals with variants in HUWE1 and suggested guidelines for clinical management. Our study includes several female cases, which have not been widely reported previously. Our findings confirm earlier reported clinical features including developmental delay, autism, hypotonia, short stature, and dysmorphic facial features as well as additional multisystemic findings. Intrauterine growth restriction (IUGR) and feeding difficulties were common in the neonatal period. It is notable that nearly all females had de novo variants, and males had de novo or inherited variants from clinically unaffected carrier mothers. Three genetic hotspots were identified in evolutionarily conserved regions of HUWE1 that have clinical impact. This report provides additional characterization of the spectrum of HUWE1-related neurodevelopmental disorder (HNDD).
DOI: 10.1002/ajmg.a.70127
Authors: Mindy H. Li, Deziree L. Coleman, Kelsey Hogan, Danielle Luz, Lindsay Bhandari, Newell Belnap, Tiffany Busa, Charles Coutton, Klaus Dieterich, Svetlana Gorokhova, Clara Hildebrandt, Rachel Logan, Milena Mariani, Manuela Morleo, Vincenzo Nigro, John Pappas, Rachel Rabin, Kelly Schoch, Angelo Selicorni, Vandana Shashi, Rebecca Spillmann, Jennifer Sullivan, Charlotte Tardy, Samantha A. Schrier Vergano, Brock Grill, Kristin Baranano
Institutions: Rush University Medical Center, University of Washington, Norcliffe Foundation, Seattle Children's Research Institute, Johns Hopkins University, Johns Hopkins Medicine, Translational Genomics Research Institute, Assistance Publique Hôpitaux de Marseille, Hôpital de la Timone, Inserm, Institut pour l'avancée des biosciences, Université Grenoble Alpes, Aix-Marseille Université, University of North Carolina at Chapel Hill, Children's Healthcare of Atlanta, Azienda Socio Sanitaria Territoriale Lariana, Ospedale Sant'Anna, University of Campania "Luigi Vanvitelli", Telethon Institute Of Genetics And Medicine, NYU Langone Health, New York University, Duke University, Duke Medical Center, Eastern Virginia Medical School, Children's Hospital of The King's Daughters
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,710
OpenAlex ID: W7154240189