Targeted gene under study:
CHAMP1 – OMIM 616327; NEDHILD – OMIM 616579
Abstract
Truncating variants in CHAMP1 were described in 40 subjects so far associated with severe ID, ASD and distinctive facial features. Whether haploinsufficiency is the underlying pathomechanism is a matter of debate. Literature deals with some 13q33q34 deletions encompassing CHAMP1, associated with a milder phenotype. One only subject with a missense variant was described, presenting with refractory epilepsy. In reporting 3 novel patients with a truncating variant, a whole gene deletion and a missense variant, respectively, we tentatively defined three categories of CHAMP1-related disorders on the basis of pathomechanisms: truncating variants cause a severe phenotype through a dominant negative effect; CHAMP1 haploinsufficiency results in a mild phenotype; certain missense variants give rise to severe epileptic encephalopathy through gain-of-function (Amenta et al, 2023). These preliminary suggestions require confirmation. Importantly, the role of missense variants is conflicting. We aim to confirm the heterogeneous nosology of CHAMP1 disease depending on pathomechanisms, by expanding the patient series in these three categories.
Coordinating clinician
Pr Marcella Zollino – marcella.zollino@unicatt.it
Institution
Institute of Genomic Medicine, Department of Life Sciences and Public Health, ‘Sacro Cuore’ Catholic University of Rome, Italy
Specific requirements beyond clinical data and genotype data sharing:
1- Re-analysis of DNA samples: Yes
2- Resampling of patients: Yes
3- Linked to a translational/basic research project: Yes