Novel heterozygous PNPT1 variant in a family with sensory ataxic neuropathy

<h3></h3> Inherited neuropathies encompass a range of diseases from those in which the neuropathy is the sole or predominant feature of the disease to those in which the neuropathy occurs as part of a multisystem disease. Individuals with sensory ataxic neuropathy (SAN) develop loss of proprioception and vibration. Recently heterozygous variants in polyribonucleotide- nucleotidyltransferase-1 (PNPT1), with incomplete penetrance and variable expressivity, have been associated with cerebellar ataxia and prominent sensory neuropathy. Clinical manifestations are variable including gait disturbance, incoordination, nystagmus, dysarthria, scoliosis, and sensory neuropathy with decreased reflexes. Barbier et al, 2022, identified novel PNPT1 variants in two families with autosomal-dominant (AD) sensory and cerebellar ataxia. Whole-genome-sequencing was performed on a family (proband and father) with AD SAN. A pathogenic nonsense (Arg715Ter) variant was detected and confirmed on sanger sequencing. They presented with a SAN with impaired pinprick, proprioception, and vibration sense. Reflexes were globally absent in proband. Additional signs included scoliosis. Neurophysiology showed a sensory neuropathy. Brain imaging showed cerebellar atrophy in proband, consistent with previous reports. <h3>Conclusion</h3> We report a novel heterozygous nonsense variant in PNPT1 in a family with SAN. This highlights the genetic and phenotypical heterogeneity of PNPT1 and identifies PNPT1 as a cause of isolated SAN.