Childhood onset hereditary spastic paraplegia

Gene: HSPD1

Green List (high evidence)

The rating of this gene has been updated to Green 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 list classification: This gene should be promoted to Green at the next GMS panel update under the AR inheritance pattern for the childhood-onset panel.

Created: 13 Apr 2022, 3:16 p.m. | Last Modified: 13 Apr 2022, 3:16 p.m.

Panel Version: 2.137

Comment on mode of inheritance: Changed from 'monoallelic' to 'biallelic' as per the review by Zornitza Stark (Australian Genomics) stating that only biallelic variants cause a more severe phenotype including spasticity with onset in childhood.

Created: 13 Apr 2022, 3:14 p.m. | Last Modified: 13 Apr 2022, 3:14 p.m.

Panel Version: 2.135

Green List (high evidence)

Bi-allelic variants cause a paediatric-onset leukodystrophy, with spasticity as a feature: this association is pertinent to this panel. Mono-allelic variants have been associated with adult-onset HSP and are pertinent to the adult panel.

Created: 19 Sep 2020, 7:32 a.m. | Last Modified: 19 Sep 2020, 7:32 a.m.

Panel Version: 2.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 4, MIM# 612233; Spastic paraplegia 13, autosomal dominant, MIM# 605280

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

I don't know

Adult onset. One clear family but also not fully penetrant. Another individual with two unaffected brothers with mutation.

Created: 10 May 2019, 11:58 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 11898127

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

I don't know

Pseudogene confounds variant calling. Publications- 1) 2 affected memebers from same family SPG, 2) 1 pt identified in a screen of 23 unrelated danish, affected pt's 2 brothers had the same mutation but no manifestations of SPG, FHX suggests mother may have been affected ?reduce penetrance. pt 3)linkage studies, followed by candidate gene analysis, of a large Israeli Bedouin family with autosomal recessive hypomyelinating leukodystrophy HLD4.

Created: 28 Apr 2019, 4:16 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Spastic paraplegia 13, autosomal dominant or pseudoautosomal, NOT imprinted, 605280; Leukodystrophy, hypomyelinating, 4, autosomal recessive, 612233

I don't know

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.

Comment on list classification: demoted from Green to Amber after internal clinical review

Created: 28 Jan 2019, 12:55 p.m.

Onset of SPG13 is variable: 3rd to 6th decade (10677329). PLease consider marking as amber following discussions with GLH

Created: 14 Jan 2019, 5:08 p.m.