Mutations in DCC cause congenital mirror movements.

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Mirror movements are involuntary movements mirroring voluntary actions, often linked to developmental defects in the central nervous system's midline crossing.
• These movements can be associated with genetic factors affecting neural development.

Purpose of the Study:

• To investigate the genetic basis of isolated congenital mirror movements inherited as an autosomal dominant trait.
• To identify the specific gene responsible for these movements in affected families.

Main Methods:

• Studied two large families (French Canadian and Iranian) with autosomal dominant congenital mirror movements.
• Performed genetic analysis to identify mutations in affected individuals.
• Conducted functional analysis of the identified mutant protein.

Main Results:

• Affected individuals in both families carried protein-truncating mutations in the DCC (deleted in colorectal carcinoma) gene.
• The DCC gene, located on chromosome 18q21.2, encodes the netrin-1 receptor, vital for axon guidance.
• Functional analysis showed the mutant DCC protein had impaired netrin-1 binding.

Conclusions:

• Mutations in the DCC gene are a cause of isolated congenital mirror movements.
• DCC plays a critical role in the lateralization of the human nervous system.
• Defects in netrin-1 signaling via DCC disrupt normal neural development and motor control.