Heterozygous PNPT1 Variants Cause a Sensory Ataxic Neuropathy

Overview

Journal Eur J Neurol

Publisher Wiley

Date 2025 Feb 10

PMID 39924761

Authors

Saif Haddad

Christopher J Record

Eleanor Self

Mariola Skorupinska

Alexander M Rossor

Matilde Laura

Gordon Ingle

Adnan Manzur

Francesco Muntoni

Julian C Blake

Mary M Reilly

Affiliations

Soon will be listed here.

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.

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