Late-onset sensory-motor axonal neuropathy, a novel SLC12A6-related phenotype.
Sissel LøsethHelle HøyerKim-Mai LeEric DelpireEinar KingeAsgeir LandeHilde Tveitan HilmarsenToril FagerheimØivind NilssenGeir Julius BraathenPublished in: Brain : a journal of neurology (2023)
We describe five families from different regions in Norway with a late-onset autosomal-dominant hereditary polyneuropathy sharing a heterozygous variant in the SLC12A6 gene. Mutations in the same gene have previously been described in infants with autosomal-recessive hereditary motor and sensory neuropathy with corpus callosum agenesis and mental retardation (Andermann syndrome), and in a few case reports describing dominantly acting de novo mutations, most of them with onset in childhood. The phenotypes in our families demonstrated heterogeneity. Some of our patients only had subtle to moderate symptoms and some individuals even no complaints. None had CNS manifestations. Clinical and neurophysiological evaluations revealed a predominant sensory axonal polyneuropathy with slight to moderate motor components. In all 10 patients the identical SLC12A6 missense variant, NM_001365088.1 c.1655G>A p.(Gly552Asp), was identified. For functional characterization, the mutant potassium chloride cotransporter 3 was modelled in Xenopus oocytes. This revealed a significant reduction in potassium influx for the p.(Gly552Asp) substitution. Our findings further expand the spectrum of SLC12A6 disease, from biallelic hereditary motor and sensory neuropathy with corpus callosum agenesis and mental retardation and monoallelic early-onset hereditary motor and sensory neuropathy caused by de novo mutations, to late-onset autosomal-dominant axonal neuropathy with predominant sensory deficits.
Keyphrases
- late onset
- early onset
- end stage renal disease
- ejection fraction
- spinal cord injury
- newly diagnosed
- chronic kidney disease
- single cell
- intellectual disability
- prognostic factors
- patient reported outcomes
- mental health
- high intensity
- blood brain barrier
- gene expression
- social media
- copy number
- dna methylation
- young adults
- health information
- transcription factor
- drug induced
- optic nerve