The DSCAM gene encodes a member of the immunoglobulin superfamily of cell adhesion molecules. Members of this family localize on the surface of cells and help in binding cells to each other or with the extracellular matrix. The DSCAM protein is specifically involved in neuronal self-avoidance, an essential mechanism during arborisation and axon branching, wherein it promotes repulsion between neuronal projections from the same type of cells in order to avoid clumping or fasciculation. By carrying out its function, DSCAM is believed to play a role in several developmental processes of the nervous system such as synapse assembly, dendrite morphogenesis, axon guidance and retina layer formation.
Overexpression or duplication of the DSCAM gene region has been linked to cases of Down Syndrome and Congenital Heart Disease (DSCHD), a condition characterized by mental retardation, characteristic facies and major congenital malformations such as atrioventricular septal defects.
The DSCAM gene is located on the long arm of chromosome 21. It spans a length of 836 kDa of DNA and its coding sequence is spread across 33 exons. The gene encodes a 222.2 kDa protein product consisting of 2012 amino acids. An additional short isoform of the DSCAM protein exists due to an alternatively spliced transcript variant. It consists of 1571 amino acids and has a molecular mass of 173.8 kDa. The gene is found to be mainly expressed in the developing nervous system.
Monies et al. (2017) described the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, a 2-year-old male, presented with growth retardation, short stature, microcephaly, fine/gross motor delay, speech delay, intellectual disability and seizures. Using whole exome sequencing, a homozygous mutation (c.4132+2T>A) was identified in exon 23 of the patient’s DSCAM gene. This gene mutation was considered a candidate for pathogenicity as it was a novel potentially truncating variant, and the gene had a well-established role in axon development. Further studies are required to independently confirm this association.
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