Hereditary neuropathy or pain disorder
Gene: ARHGEF10
PMID:14508709 reported the identification of p.Thr109Ile variant in ARHGEF10 gene in a four-generation family presenting with slowed nerve conduction velocity without the clinical phenotype of hereditary motor and sensory neuropathy. This has already been reported in OMIM (MIM #608236). Functional analysis showed that residue 332 is located in the negative regulatory region in the N terminus and the T332I mutant is constitutively active and it is similar to the N-terminal truncated mutant (PMID:21719701).
PMID:25025039 reported the identification of a novel likely pathogenic variant p.Arg338Thr in one of 81 Norwegian families with Charcot-Marie-Tooth disease.
PMID:25275565 reported that a 10bp deletion in ARHGEF10 gene is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs. However, Arhgef10-depleted mice developed an autism spectrum disorder-like phenotype.Created: 1 May 2023, 9:25 a.m. | Last Modified: 1 May 2023, 9:25 a.m.
Panel Version: 3.21
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
?Slowed nerve conduction velocity, AD, OMIM:608236
Publications
Not enough evidenceCreated: 24 Nov 2022, 6:23 p.m. | Last Modified: 24 Nov 2022, 6:23 p.m.
Panel Version: 1.105
Single family reported in 2003 with slowed nerve conduction velocities but no other clinical findings. Two others in CMT cohorts, plus functional data.Created: 31 Mar 2020, 7:18 a.m. | Last Modified: 31 Mar 2020, 7:18 a.m.
Panel Version: 1.4
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Slowed nerve conduction velocity, MIM# 608236
Publications
Only a single reported familyCreated: 10 May 2019, 12:54 p.m.
In Bristol lots of C3s, no strong candidates. PMID: 14508709 Verhoeven (2003) Functional studies show that the Thr332Ile mutant stimulates increased actomyosin contraction, regulating cell morphology in Schwann cells. Most others on HGMD are exome papers.Created: 29 Apr 2019, 12:30 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
?Slowed nerve conduction velocity, AD, 608236
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Re-evaluation of evidence - demotion / One published family plus functional evidence (NB. Bristol review although Green acknowledges limited evidence) - demoteCreated: 6 Dec 2019, 2:17 p.m. | Last Modified: 6 Dec 2019, 2:17 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, 1:14 p.m. | Last Modified: 6 Dec 2019, 1:16 p.m.
Panel Version: 0.7
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.
Only one published familyCreated: 29 Apr 2019, 9:20 a.m.
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Comment on list classification: Promoted from red to green due to agreement from 3 reviewers.Created: 4 May 2016, 9:35 a.m.
Publications for gene: ARHGEF10 were set to 14508709
Gene: arhgef10 has been classified as Amber List (Moderate Evidence).
gene: ARHGEF10 was added gene: ARHGEF10 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH,Expert list,UKGTN,Expert Review Green,South West GLH Mode of inheritance for gene: ARHGEF10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARHGEF10 were set to 14508709 Phenotypes for gene: ARHGEF10 were set to ?Slowed nerve conduction velocity, AD, 608236