Heterozygous PNPT1 Variants Cause a Sensory Ataxic Neuropathy

Abstract

Background

Biallelic variants in polyribonucleotide-nucleotidyltransferase-1 (PNPT1) have been associated with a range of phenotypes from syndromic hearing loss to Leigh's syndrome. More recently, heterozygous variants in PNPT1, have been reported in three families with cerebellar ataxia and prominent sensory neuropathy.

Methods

Whole genome sequencing was performed in two families with autosomal dominant sensory ataxic neuropathy (SAN).

Results

Segregating heterozygous splice site (c.2014-3C>G) and nonsense (p.Arg715Ter) variants were detected in both families. All patients initially presented with an isolated SAN clinically and neurophysiologically with subsequent variable cerebellar involvement.

Conclusion

We report two heterozygous PNPT1 variants in two families with a predominant SAN, including the novel p.Arg715Ter. This strengthens the argument of PNPT1 causing dominant disease and highlights a new cause for dominantly inherited SAN.