Hereditary neuropathy or pain disorder
Gene: ATL3
Autosomal dominant HSN, several families described . Previous recessive entry was an errorCreated: 16 May 2019, 12:02 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Literature search 6th May 2016, 2 articles found PMID: 24459106 c.575A>G (p.Tyr192Cys) heterozygous segregated with affected family members in a German family and Spanish family with hereditary sensory and autonomic neuropathies type 1, Haplotype analysis at the ATL3 locus of both families suggested that they share the same alleles compatible with identity by descent; PMID:24736309 - report of a Bosnian family, in which father and son with hereditary sensory neuropathy type 1 were heterozygous for ATL3 c.1013C>G p.Pro338Arg, that was not found in unaffected sonCreated: 29 Apr 2019, 12:30 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Re-evaluation of evidence - demotion / Limited evidence highlighted by Natalie - same variant in 2 families and other variant didn't segregate - downgrade to Amber? Agree downgrade due to lack of evidenceCreated: 6 Dec 2019, 2:16 p.m. | Last Modified: 6 Dec 2019, 2:16 p.m.
Panel Version: 0.35
Comment on list classification: 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, 1:17 p.m. | Last Modified: 6 Dec 2019, 1:17 p.m.
Panel Version: 0.8
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
Comment when marking as ready: 24459106 and 24736309 both demonstrate monoallelic (AD) inheritanceCreated: 8 Jul 2016, 3:22 a.m.
Comment on mode of inheritance: The literature reports and OMIM state monoallelic inheritance (variants found in a heterozygous state), but both reviewers suggested biallelic.Created: 6 May 2016, 8:26 a.m.
Comment on list classification: A reviewer added the gene, and a second reviewer rated this green.Created: 6 May 2016, 8:24 a.m.
Gene: atl3 has been classified as Amber List (Moderate Evidence).
gene: ATL3 was added gene: ATL3 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH,South West GLH,Expert Review Green,Expert Review Mode of inheritance for gene: ATL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATL3 were set to 24459106; 24736309