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 (2022)
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 central nervous system manifestations. Clinical and neurophysiological evaluations revealed a predominant sensory axonal polyneuropathy with slight to moderate motor components. In all ten 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
- spinal cord injury
- ejection fraction
- chronic kidney disease
- newly diagnosed
- single cell
- peritoneal dialysis
- case report
- photodynamic therapy
- healthcare
- dna methylation
- traumatic brain injury
- depressive symptoms
- young adults
- optic nerve
- physical activity
- optical coherence tomography
- early life