Hereditary spastic paraplegia - childhood onset
Gene: HSPD1
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
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
Variants in this GENE are reported as part of current diagnostic practice
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
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 reviewCreated: 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 GLHCreated: 14 Jan 2019, 5:08 p.m.
Publications for gene: HSPD1 were set to 17420924; 10677329
Source Yorkshire and North East GLH was added to HSPD1.
Source NHS GMS was added to HSPD1.
Source London North GLH was added to HSPD1.
Added phenotypes Spastic paraplegia 13, autosomal dominant, 605280 for gene: HSPD1
Arianna Tucci: Onset of SPG13 is variable: 3
Phenotypes for gene: HSPD1 were changed from Spastic paraplegia 13, autosomal dominant; 605280 to Spastic paraplegia 13, autosomal dominant, 605280
Phenotypes for gene: HSPD1 were changed from Spastic paraplegia 13, autosomal dominant to Spastic paraplegia 13, autosomal dominant; 605280
Publications for gene: HSPD1 were set to Hansen et al. (2002)
Gene: hspd1 has been classified as Amber List (Moderate Evidence).
gene: HSPD1 was added gene: HSPD1 was added to Hereditary spastic paraplegia - childhood onset. Sources: Radboud University Medical Center, Nijmegen,UKGTN,Expert list,Expert Review Green,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: HSPD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: HSPD1 were set to Hansen et al. (2002) Phenotypes for gene: HSPD1 were set to Spastic paraplegia 13, autosomal dominant