There are genetic variations among children with a rare neurodevelopmental disease, according to a new study headed by the Seaver Autism Center for Study and Treatment at Mount Sinai. This discovery could set the path for a precision medicine approach to treating these children.
The study is the first of its type to explicitly evaluate differences between people with CHAMP1 gene mutations and those with gene deletions. On July 17th, 2023 the study was released in Human Genetics.
A hereditary neurodevelopmental disease called CHAMP1 disorder is accompanied by intellectual disability, medical comorbidities (including seizures and gastrointestinal issues), and dysmorphic traits. The CHAMP1 gene’s mutations or deletions are responsible for the disease.
Two sets of participants were clinically evaluated by researchers from the Seaver Autism Center: 16 people with CHAMP1 coding mutations (spelling changes in the gene) and 8 people with CHAMP1 deletions.
All domains of adaptive functioning, including communication, daily living skills, sociability, and motor skills, showed substantially worse adaptive functioning skills in the CHAMP1 gene mutation group than in the deletion group.
The mutant group also showed more severe developmental delays, reduced muscle tone, and gastrointestinal problems than the mutation group.
The variance in symptoms, according to researchers, is most likely caused by distinct processes underlying the deletions and mutations of the CHAMP1 gene. Deletions affect the body through CHAMP1 haploinsufficiency, which happens when the one functional copy of the CHAMP1 gene is insufficient to maintain the body’s normal function.
To actively interfere with the operation of the normal gene and produce more severe clinical symptoms, mutations may work through dominant negative or gain-of-function mechanisms.
Hearing parents describe the challenges and strengths their children experience and possess has showed us that while these children share the diagnosis of CHAMP1 disorder, their presentations and behaviors often differ.”
Thariana Pichardo, Clinical Research Coordinator, Seaver Autism Center
The findings of the study highlight the significance of comprehending the processes of mutations and deletions before developing treatments for CHAMP1 and other diseases, such as autism, that have varied genetic origins and a wide range of diagnostic criteria.
This analysis unveils valuable insight into potential therapeutics that may lead to successful symptom improvement. Pinpointing the mechanisms that are the source of this disorder will enable a precision medicine approach to treatment for the two groups of patients with different presentation but ultimately the same CHAMP1 disorder diagnosis.”
Tess Levy, Study First Author and Assistant Professor, Psychiatry, Icahn School of Medicine, Mount Sinai Health System
Levy, T., et al. (2023). Prospective phenotyping of CHAMP1 disorder indicates that coding mutations may not act through haploinsufficiency. Human Genetics. doi.org/10.1007/s00439-023-02578-6