A homozygous variant, p.I63N (c.188T > A), in the <i>HINT1</i> gene was found in both brothers.<h4>Conclusion</h4>We describe a novel, likely pathogenic, <i>HINT1</i> pI63N (c.188T > A) homozygous variant associated with hereditary axonal motor-predominant neuropathy without neuromyotonia in two African American brothers. Here, HINT1 is linked to Isaacs syndrome.