Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Ppublish 5 citations
PubMed: 36542484 DOI: 10.1093/brain/awac488
Late-onset sensory-motor axonal neuropathy, a novel SLC12A6-related phenotype.
Brain 146(3):912-922
Authors: Sissel Løseth, Helle Høyer, Kim-Mai Le, Eric Delpire, Einar Kinge, Asgeir Lande, Hilde Tveitan Hilmarsen, Toril Fagerheim, Øivind Nilssen, Geir Julius Braathen
Affiliations
- Department of Neurology and Clinical Neurophysiology, University Hospital of North Norway, 9019 Tromsø, Norway.
- Department of Clinical Medicine, The Arctic University of Norway, 9019 Tromsø, Norway.
- Department of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.
- Department of Neurology and Clinical Neurophysiology, Medical Division, Akershus University Hospital, 1478 Lørenskog, Norway.
- Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
- Sandvika Neurocenter, 1337 Sandvika, Norway.
- Department of Medical Genetics, Oslo University Hospital, 0450 Oslo, Norway.
- Department of Medical Genetics, Division of Child and Adolescent Health, University Hospital of North-Norway, 9019 Tromsø, Norway.
Abstract
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.
MeSH
Polyneuropathies, Hereditary Sensory And Motor Neuropathy, Mutation, Neurology, Genes, Intellectual Disability, Phenotype, Agenesis Of Corpus Callosum