Background: De novo pathogenic variants in CHAMP1 (chromosome alignment maintaining phosphoprotein 1) that encodes kinetochore-microtubule associated protein on 13q34 cause a rare neurodevelopmental disorder. Methods: We enrolled 14 individuals with pathogenic variants in CHAMP1 that were documented by exome sequencing or gene panel sequencing. Medical history interviews, seizure surveys, Vineland Adapted Behavior Scales Second Edition, and other behavioral surveys were completed by primary care givers of available participants in Simons Searchlight. Clinicians extracted clinical data from the medical record for two participants. Results: We report on clinical features of fourteen individuals (ages 2-26) with de novo predicted loss of function variants in CHAMP1 and compare them with previously reported cases (total n=32). At least two individuals have the same de novo variant: p.(Ser181Cysfs*5), p.(Trp348*), p.(Arg398*), p.(Arg497*), or p.(Tyr709*). Common phenotypes include intellectual disability/developmental delay, language impairment, congenital and acquired microcephaly, behavioral problems including autism spectrum disorder, seizures, hypotonia, gastrointestinal issues of reflux and constipation, and ophthalmologic issues. Other rarely observed phenotypes include leukemia, failure to thrive and high pain tolerance. Conclusion: Pathogenic variants in CHAMP1 are associated with a variable clinical phenotype of developmental delay/intellectual disability and seizures.
Intellectual disability; Severe global developmental delay; Severe microcephaly
Garrity M, Kavus H, Rojas-Vasquez M, Valenzuela I, Larson A, Reed S, et al. Neurodevelopmental Phenotypes in Individuals with Pathogenic Variants in CHAMP1. Cold Spring Harb Mol Case Stud. 2021 Aug;7(4):a006092.
Use this identifier for quote and/or link this documenthttp://hdl.handle.net/11351/7260
This item appears in following collections
- HVH - Articles científics 
The following license files are associated with this item: