Adult onset hereditary spastic paraplegia

Gene: TFG

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 14 Mar 2022, 1:19 p.m. | Last Modified: 14 Mar 2022, 1:19 p.m.

Panel Version: 1.95

Review of literature did not reveal any adult onset cases - childhood onset only.

The 'Q3_21_phenotype' tag has been added to highlight that this is a childhood onset condition. Leaving the rating as Green, but with a recommendation for review at the next GMS panel update. This gene is already Green on the 'Hereditary spastic paraplegia - childhood onset v.2.18' panel.

Created: 23 Aug 2021, 9:41 a.m. | Last Modified: 23 Aug 2021, 9:41 a.m.

Panel Version: 1.49

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 57, autosomal recessive, OMIM:615658

Publications

• 23479643
• 27492651
• 27601211
• 28124177
• 29971521
• 30467354
• 33767317

Red List (low evidence)

Childhood onset.

Created: 22 Sep 2020, 5:27 a.m. | Last Modified: 22 Sep 2020, 5:27 a.m.

Panel Version: 1.7

Green List (high evidence)

Childhood onset, at least four families. No additional patients identified using Sheffield panel.

Created: 10 May 2019, 10:28 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 23479643, 27601211, 28124177
• 27492651

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Will include in local HSP panel Beetz (2013, 23479643) Initial report. Exome study, 2 sibs with early-onset spastic paraplegia, optic atrophy, and neuropathy, with hom c.316C>T (p.R106C). In vitro defect shown in self-assembly. Harlalka (2016, 27492651) also described a c.317G>A (p.R106H) homozygous family, and proposed a founder origin for the c.316C>T variant, as well as a c.316_317 hotspot. further mt invitro studies supportive evidence. Elsayed (2016, 27601211) implicated TGF in one family; homozygous c.64C>T (p.(Arg22Trp) with HSP. In Sheffield diagnostic HSP panel.

Created: 27 Apr 2019, 4:17 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• Beetz (2013) 23479643

I don't know

Review and rating submitted byJames Polke (Neurogenetics Laboratory,Institute of Neurology, London), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.

Created: 9 May 2019, 4:50 p.m.

Review and rating from Chris Buxton (North Bristol NHS Trust), submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.

Created: 27 Apr 2019, 4:30 p.m.

Green List (high evidence)

may have optic atrophy and peripheral neuropathy, 2 sibs from 1 family published with AR SPG 57. affected members of 4 Japanese families & 16 affected members of a large multigenerational Taiwanese family with Okinawa hereditary motor and sensory neuropathy; Vicotria: Green. In sheffield HSP panel

Created: 25 Apr 2019, 1:22 p.m.

Phenotypes
?Spastic paraplegia 57, autosomal recessive 615658,AR; Hereditary motor and sensory neuropathy, Okinawa type, 604484, AD