Optical Genome Mapping Reveals Disruption of the RASGRF2 Gene in a Patient with Developmental Delay Carrying a De Novo Balanced Reciprocal Translocation

• Published in: Genes 2024-06, Vol.15 (6), p.809
• Main Authors: Lederbogen, Rosa Catalina, Hoffjan, Sabine, Thiels, Charlotte, Mau-Holzmann, Ulrike Angelika, Singer, Sylke, Yusenko, Maria Viktorovna, Nguyen, Hoa Huu Phuc, Gerding, Wanda Maria
• Format: Article
• Language: English
• Subjects: Behavioral plasticity; Child development; Chromosome 5; Chromosome 6; Chromosome Mapping; Chromosome translocations; Chromosomes; Chromosomes, Human, Pair 5 - genetics; Developmental delay; Developmental Disabilities - genetics; Developmental Disabilities - pathology; Gene mapping; Genes; Genetic aspects; Genetic engineering; Genetic testing; Genomes; Genomics; Humans; Intellectual disabilities; Intellectual Disability - genetics; Intellectual Disability - pathology; Kinases; Labeling; Male; Mental retardation; Neurodevelopment; Neurodevelopmental disorders; Neurophysiology; Peptide mapping; Proteins; ras Guanine Nucleotide Exchange Factors - genetics; Ras protein; Synaptic plasticity; Translocation, Genetic
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes15060809

While balanced reciprocal translocations are relatively common, they often remain clinically silent unless they lead to the disruption of functional genes. In this study, we present the case of a boy exhibiting developmental delay and mild intellectual disability. Initial karyotyping revealed a translocation t(5;6)(q13;q23) between chromosomes 5 and 6 with limited resolution. Optical genome mapping (OGM) enabled a more precise depiction of the breakpoint regions involved in the reciprocal translocation. While the breakpoint region on chromosome 6 did not encompass any known gene, OGM revealed the disruption of the (Ras protein-specific guanine nucleotide releasing factor 2) gene on chromosome 5, implicating as a potential candidate gene contributing to the observed developmental delay in the patient. Variations in have so far not been reported in developmental delay, but research on the gene underscores its significance in various aspects of neurodevelopment, including synaptic plasticity, signaling pathways, and behavioral responses. This study highlights the utility of OGM in identifying breakpoint regions, providing possible insights into the understanding of neurodevelopmental disorders. It also helps affected individuals in gaining more knowledge about potential causes of their conditions.