Childhood onset hereditary spastic paraplegia

Gene: TFG

The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 2:55 p.m. | Last Modified: 1 Feb 2023, 2:55 p.m.

Panel Version: 3.9

Comment on mode of inheritance: MOI should be changed from 'both mono- and biallelic' to 'biallelic' only at the next GMS panel update.

Monoallelic variants are associated with an adult onset neuropathy (MIM# 604484), a disorder that does not include spasticity and is therefore not relevant to this panel.

Created: 23 Aug 2021, 9:03 a.m. | Last Modified: 23 Aug 2021, 9:03 a.m.

Panel Version: 2.68

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

I don't know

Amber gene with Green GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.

Created: 21 May 2019, 4:50 p.m.

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, 4:54 p.m.

Amber rating on Hereditary spastic paraplegia panel 1.198

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
Chris Buxton (North Bristol NHS Trust), 27 Nov 2018. Submitted Green review.


Comment when marking as ready: Single Indian family currently described in association with HSP
emma baple (Genomics England Curator), 10 May 2016

Created: 2 May 2019, 4:56 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: 28 Apr 2019, 4:16 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

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