Abstract

Abstract Background Spinocerebellar ataxia with axonal neuropathy type 1 (OMIM: 607250) is an extremely rare autosomal recessive disorder caused by a mutation in the tyrosyl-DNA phosphodiesterase 1 ( TDP1) gene. Only a single missense variant (p.His493Arg) in this gene has been reported. This variant was found in three Arab families with a possible common founder effect. Methods and Results We report a female patient born to a consanguineous Pakistani family segregating autosomal recessive spinocerebellar ataxia with axonal neuropathy type 1. The patient presents additional clinical features distinct from previously reported Arab families including congenital onset of the disease. We performed whole exome sequencing with the patient’s DNA and identified a novel missense variant (NC_000014.9:g.89991982C > T; p.His478Tyr) in exon 13 of the TDP1 gene. Sanger sequencing was performed to verify the autosomal recessive segregation of the p.His478Tyr variant in the family. Conclusion The current study expands both the clinical and mutation spectrum of the TDP1 associated spinocerebellar ataxia with axonal neuropathy type 1 and increases the body of evidence that supports the pathogenic role of TDP1 in cerebellar ataxias with peripheral neuropathy.