Identifying the Potential Role of Missense <scp> <i>KIRREL3</i> </scp> Variants in Neurodevelopmental Phenotypes: A Case Series
Neurodevelopmental disorders encompass a large group of conditions, many of which can be explained by genetic variants. KIRREL3 has previously been associated with neurodevelopmental disorders and is expressed in the developing human basal ganglia and amygdala. Through GeneMatcher, which allows clinicians, families, and researchers to share information about novel gene variants, and the Simons Foundation Powering Autism Research (SPARK) project, we identified 26 individuals with different rare missense variants in KIRREL3, which were predicted to be damaging based on their REVEL score. All probands had neurodevelopmental diagnoses including autism spectrum disorder, global developmental delay, intellectual disability, or a learning disability. A full review of previous publications identified 10 rare KIRREL3 missense variants in 13 individuals who had at least one diagnosis of an autism spectrum disorder or intellectual disability. These findings highlight the potential role of KIRREL3 missense variants in neurodevelopmental disorders, which warrants further study.
Authors
- Sharon Chen (ORCID: https://orcid.org/0000-0002-0576-0856)
- David D. Weaver (ORCID: https://orcid.org/0000-0002-8312-8995)
- Alpa Sidhu (ORCID: https://orcid.org/0000-0002-8980-5029)
- Sabah Sabir
- Marta Frigeni (ORCID: https://orcid.org/0000-0001-8544-7175)
- Sarah U. Morton (ORCID: https://orcid.org/0000-0002-7816-2646)
- Qifei Li (ORCID: https://orcid.org/0000-0002-0069-8512)
- Marcia V. Felker (ORCID: https://orcid.org/0000-0002-8287-024X)
- Jaclyn Kotlarek
- Amy E. Roberts (ORCID: https://orcid.org/0000-0001-5827-8521)
- Shayna Svihovec (ORCID: https://orcid.org/0000-0002-9359-1916)
- Pankaj B. Agrawal (ORCID: https://orcid.org/0000-0003-3255-0456)
- Lisa R. Sun (ORCID: https://orcid.org/0000-0003-4948-0415)
- Katherine Anderson (ORCID: https://orcid.org/0000-0002-2369-8304)
- Ryan Doan
- Margarita Sáenz
- Joan Stoler
- Divya Jayvas
- Christine Giummo
- Krista Schatz
- Priyanka R. Narayan (ORCID: https://orcid.org/0000-0001-6116-2087)
Institutions
- Boston Children's Hospital (US)
- Harvard University (US)
- Hofstra University (US)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- University of Vermont Medical Center (US)
- Jackson Health System (US)
- University of Miami Hospital (US)
- University of Iowa Health Care (US)
- Indiana University School of Medicine
- Indiana University – Purdue University Indianapolis (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- American Journal of Medical Genetics Part A
- Published
- 2026-08-13
- DOI
- https://doi.org/10.1002/ajmg.a.70264
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00