Hereditary neuropathy or pain disorder
Gene: SLC12A6This gene is still currently under NHSE review. Tagging again to highlight the new review submitted by Christopher Record (UCL) indicating this gene should be made Green under the 'Both mono- and biallelic' MOI. Both phenotypes are included in OMIM (MIM# 218000; MIM# 620068) and the biallelic form is listed in Gene2Phenotype with a 'definitive' disease confidence category.Created: 3 Jan 2024, 11:44 a.m. | Last Modified: 3 Jan 2024, 11:44 a.m.
Panel Version: 3.68
>15 families with dominant or de novo dominant CMT. Should be in panel certainly for AD CMT.
The more complex recessive disease includes a clear neuropathy phenotype but additional features. Probably should also be included as green gene in AR formCreated: 9 Nov 2023, 12:33 p.m. | Last Modified: 9 Nov 2023, 12:33 p.m.
Panel Version: 3.62
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
CMT1, CMT2, CMTi, dHMN
Publications
The to_be_confirmed_NHSE tag has been added, as further NHSE review is required.Created: 15 Mar 2022, 3:49 p.m. | Last Modified: 15 Mar 2022, 3:49 p.m.
Panel Version: 1.88
In reviewing SLC12A6 on the Intellectual disabily panel, it was suggested that this gene should be green on this panel (source NHS Genomic Medicine Service).Created: 3 Feb 2022, 2:13 p.m. | Last Modified: 3 Feb 2022, 2:13 p.m.
Panel Version: 1.80
For-review tag has been added as it maybe appropriate to change the MOI to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next major review, to ensure that de novo heterozgous variants are identified.Created: 13 Jul 2020, 3:33 p.m. | Last Modified: 13 Jul 2020, 3:33 p.m.
Panel Version: 1.6
Associated with Agenesis of the corpus callosum with peripheral neuropathy 218000 in OMIM and as confirmed Gen2Phen gene. At least 10 biallelic variants were reported in at least 10 unrelated cases. 9/10 of these variants was terminating (PMID 12368912, 16606917, 17893295). Three de novo heterozygous missense variants have been identified in four unrelated cases with a milder phenotype of early- onset progressive Charcot- Marie-tooth disease (CMT) with or without spasticity (intermediate CMT)(PMID 31439721, 27485015). The authors of PMID 31439721 suggest that "autosomal- dominant inheritance of SLC12A6 variants also needs to be considered in patients with early- onset neuropathies". Furthermore, it will be important to understand the functional differences between the variants, as PMID 27485015 reported variant - p.Thr991Ala, resulted in increased potassium influx in Xenopus oocytes (gain-of-function), while the other missense variants identified so far had a loss-of-function effect in varying degrees (PMID 31439721).Created: 13 Jul 2020, 3:33 p.m. | Last Modified: 13 Jul 2020, 3:33 p.m.
Panel Version: 1.6
2 unrelated patients with reported variants in Bristol. In one family two affected sibs were both found to be compound heterozygous. PMID: 12368912 - reported mice with a targeted deletion of the Slc12a6 gene had a locomotor deficit, peripheral neuropathy, and a sensorimotor gating deficit, similar to the human diseaseCreated: 29 Apr 2019, 12:30 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Gene included in a list of complex neuropathy syndrome genes recommended to be downgraded for R78 panel (list submitted by Alex Rossor 15th July 2019)Created: 6 Dec 2019, 8:28 p.m. | Last Modified: 6 Dec 2019, 8:28 p.m.
Panel Version: 0.66
This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.Created: 6 Dec 2019, 8:27 p.m. | Last Modified: 6 Dec 2019, 8:27 p.m.
Panel Version: 0.65
Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.Created: 9 May 2019, 5 p.m.
Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.Created: 29 Apr 2019, 12:53 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Complex phenotype, notpure CMTCreated: 9 Dec 2015, 8:49 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Complex phenotype, notpure CMTCreated: 8 Dec 2015, 3:05 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC12A6 were changed from Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum to Charcot-Marie-Tooth disease, axonal, type 2II, OMIM:620068; Agenesis of the corpus callosum with peripheral neuropathy, OMIM:218000
Publications for gene: SLC12A6 were set to 12368912; 31439721; 27485015; 16606917; 17893295; 21628467
Tag Q4_23_promote_green tag was added to gene: SLC12A6. Tag Q4_23_NHS_review tag was added to gene: SLC12A6.
Tag Q1_22_rating was removed from gene: SLC12A6.
Tag to_be_confirmed_NHSE tag was added to gene: SLC12A6.
Tag Q1_22_rating tag was added to gene: SLC12A6.
Publications for gene: SLC12A6 were set to 12368912
Tag for-review tag was added to gene: SLC12A6.
Gene: slc12a6 has been classified as Amber List (Moderate Evidence).
gene: SLC12A6 was added gene: SLC12A6 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,Illumina TruGenome Clinical Sequencing Services,London North GLH,Expert list,Emory Genetics Laboratory,UKGTN,Expert Review Green,South West GLH Mode of inheritance for gene: SLC12A6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC12A6 were set to 12368912 Phenotypes for gene: SLC12A6 were set to Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum