Spinocerebellar ataxia with axonal neuropathy type 1 revisited

Patrick Scott, Adila AlKindi, A. Al Fahdi, Naeema Al Yarubi, Zandre Bruwer, S. Al Adawi, Ramachandiran Nandhagopal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1; OMIM #607250), an exceedingly rare disorder having been documented in only a single family from Saudi Arabia, is the result of an unusual mutation in the tyrosyl DNA phosphodiesterase 1 gene (TDP1). We performed high-throughput sequencing (whole exome and ataxia gene panel) in two apparently unrelated Omani families segregating sensorimotor neuropathy and ataxia in an autosomal recessive fashion. Following validation by Sanger sequencing, all affected subjects (n = 4) were confirmed to carry the known SCAN1 pathogenic homozygous variant in the TDP1 gene, NM_001008744.1:c.1478A > G (p.His493Arg). In keeping with the initial description, our patients demonstrated progressive ataxia, cerebellar atrophy and disabling axonal sensori-motor neuropathy (n = 4), hypercholesterolemia (n = 2) and elevated serum alpha fetoprotein (n = 3). In addition, our patients also had mild cognitive deficits in multiple domains (n = 3), a feature not previously reported. Our findings independently revalidate the phenotype of TDP1 mutation and expand the clinical spectrum to include mild cognitive deficits. Haplotype sharing, as determined by DNA microarray (CytoScan HD), attests to a possible common founder mutation in the Arab population.

Original languageEnglish
Pages (from-to)139-144
Number of pages6
JournalJournal of Clinical Neuroscience
Volume67
DOIs
Publication statusPublished - Sep 2019

Keywords

  • Distal motor sensory neuropathy
  • Recessive ataxia
  • TDP1 mutation

ASJC Scopus subject areas

  • Surgery
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

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