Hereditary neuropathy or pain disorder
Gene: SPG7
Pathogenic variant in the homozygous state in a patient with a history of high steppage gait and foot drop in teens. Patient has sensory and motor neuropathy. Nerve conduction studies show that neuropathy is largely confined to lower limbs. Referred for R78 WGS as "likely atypical CMT2".Created: 1 Mar 2024, 11:05 a.m. | Last Modified: 1 Mar 2024, 11:05 a.m.
Panel Version: 3.83
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
sensory neuropathy; motor neuropathy; lower-limb neuropathy
Associated with OMIM:607259 and as definitive Gen2Phen gene for the same condition. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomalCreated: 11 Apr 2023, 1:55 p.m. | Last Modified: 11 Apr 2023, 1:56 p.m.
Panel Version: 3.9
Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Broader phenotype submitted by Alex Rossor, but 2 reviews say no clear association with neuropathyCreated: 7 Dec 2019, 12:03 a.m. | Last Modified: 7 Dec 2019, 12:03 a.m.
Panel Version: 0.86
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, 10:25 p.m. | Last Modified: 6 Dec 2019, 10:25 p.m.
Panel Version: 0.84
Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.Created: 11 Jun 2019, 1:40 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.
Unable to find any evidence of clear neuropathy associationCreated: 29 Apr 2019, 12:30 p.m.
Phenotypes
Hereditary Neuropathies
We have a large cohort of over 50 SPG7 patients and detected no clear peripheral neuropathyCreated: 9 Dec 2015, 4:48 p.m.
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spastic paraplegia, optic atrophy, ataxia and sensory-motor axonal neuropathy in some patients
Not a CMT geneCreated: 8 Dec 2015, 3:06 p.m.
Publications for gene: SPG7 were set to
Mode of inheritance for gene: SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: SPG7 were changed from Hereditary Neuropathies; Spastic paraplegia, optic atrophy, ataxia and sensory-motor axonal neuropathy in some patients to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Source Expert Review Amber was added to SPG7. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
gene: SPG7 was added gene: SPG7 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Emory Genetics Laboratory,South West GLH,London North GLH,NHS GMS Mode of inheritance for gene: SPG7 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SPG7 were set to Hereditary Neuropathies; Spastic paraplegia, optic atrophy, ataxia and sensory-motor axonal neuropathy in some patients