RNF170 mutation causes autosomal dominant sensory ataxia with variable pyramidal involvement

Area of Science:

• Genetics
• Neurology

Background:

• Hereditary ataxias present diverse clinical and genetic features.
• Identifying specific gene-phenotype correlations aids genetic testing and interpretation.

Purpose of the Study:

• To investigate the genetic basis of autosomal dominant sensory ataxia in a Belgian family.
• To screen for RNF170 variants in a cohort of patients with neuromuscular disorders.

Main Methods:

• Clinical evaluation of a family with sensory ataxia and pyramidal signs.
• Targeted clinical exome sequencing to identify causative genes.
• Retrospective screening of 404 neuromuscular disorder patients for RNF170 variants.

Main Results:

• A heterozygous p.Arg199Cys variant in the RNF170 gene was found in all affected family members.
• Sensory ataxia was a consistent finding, with variable pyramidal involvement and neuropathy.
• No additional pathogenic RNF170 variants were detected in the neuromuscular cohort.

Conclusions:

• The p.Arg199Cys variant in RNF170 is associated with autosomal dominant sensory ataxia and variable pyramidal involvement.
• This genotype-phenotype correlation is clinically recognizable and warrants RNF170 testing.
• Neurologists should consider RNF170 in genetic panels for ataxia and hereditary spastic paraplegia (HSP).