Snijders Block-Campeau syndrome
What is SBCS?
SBCS is a recently discovered genetic neurodevelopmental disorder, first described in 2018 by clinical researchers Lot Snijders Blok and Philippe Campeau. Individuals with this syndrome typically present with intellectual disability ranging from mild to severe, developmental delay, and speech impairments. Distinctive facial features are commonly observed, including a broad forehead, high hairline, hypertelorism (widely spaced eyes), epicanthal folds, and a broad nasal tip. Other physical characteristics may include heart defects, skeletal anomalies such as scoliosis, and urogenital abnormalities. Behavioral challenges, including autism spectrum disorder traits, attention deficit hyperactivity disorder (ADHD), and anxiety, are also frequently reported in affected individuals
What are molecular causes of SBCS?
CHD3 gene is located on 17 chromosome, while corresponding mRNA before splicing is about 28,000 base pairs and about 7,400 after. ATPase domain is the most important part of the CHD3 protein, where most mutations are found.
Gene therapy solutions for SBCS treatment
As of today, there are no reports on design and testing of gene-therapeutic solutions for SBCS. The size of the cRNA (ca. 7 kbp) creates an obvious limitation for straightforward application of AAV vectors. However, increased capacity AAC vectors, as well as bipartite approach utilizing two separate AAV carrying 5’- and 3’-portions of the cRNA, might be a solution. CRISPR-Cas9-based approach might also be utilized as a “personalized treatment” to edit the mutant fragment of CHD3 reverting it to the non-mutated form.
So far, it is known that SBCS is caused by de novo mutations in CHD3 gene found in 17th chromosome. CHD3 codes for a chromodomain-helicase-DNA-binding protein 3, involved in histone deacetylation and thus in chromatin remodeling [13]. It is speculated that the lack of CHD3 leads to the delays in expression of important neurodevelopmental genes, that remain unknown. CHD3 is expressed in form of at least three mRNA ca. 7 kbp in length. More research is required to understand the role of CHD3 in pathogenesis