Novel NUDT2 variant causes intellectual disability and polyneuropathy

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Genetic etiologies for global developmental delay, intellectual disability, and sensorimotor neuropathy are actively researched.
• The NUDT2 gene has been previously implicated in intellectual disability.

Observation:

• Exome or genome sequencing was utilized to investigate the genetic basis of neurodevelopmental and neurological disorders in two unrelated families.
• Affected individuals presented with global developmental delay, intellectual disability, and sensorimotor neuropathy characterized by distal weakness.

Findings:

• A homozygous frameshift variant (c.186delA, p.A63Qfs*3) in the NUDT2 gene was identified in affected individuals across both families.
• This finding implicates NUDT2 variants in a broader spectrum of neurological conditions than previously understood.

Implications:

• The NUDT2 gene is associated with a more complex phenotype including sensorimotor polyneuropathy with demyelinating and/or axonal features.
• This expands the diagnostic possibilities for patients presenting with these combined neurological symptoms.
• Further research into NUDT2 function may elucidate mechanisms underlying neurodevelopment and peripheral nerve integrity.