Adult onset hereditary spastic paraplegia
Gene: HSPD1
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.Created: 1 Feb 2023, 4:14 p.m. | Last Modified: 1 Feb 2023, 4:14 p.m.
Panel Version: 2.7
Comment on list classification: The evidence for this gene-disease association is borderline as only 2 families have been reported to date with HSPD1-related AD adult-onset SPG which may be associated with variable penetrance. However, this phenotype is likely best represented by the R60 panel which may justify its inclusion to minimise risk of missing diagnoses - this will be flagged for GMS discussion to determine the most appropriate classification given the current evidence.Created: 13 Apr 2022, 3:42 p.m. | Last Modified: 13 Apr 2022, 3:42 p.m.
Panel Version: 1.101
Monoallelic variants have been associated with adult-onset HSP (SPG13, MIM# 605280) and are pertinent to this adult panel. To date, only two pathogenic heterozygous missense variants in the HSPD1 gene have been identified: p.V72I in seven affected adults from a French family (PMIDs: 10677329, 11898127) and p.Q461E in a 58-year-old Danish woman (PMID: 17420924). In both families, the disease was transmitted as a late-onset autosomal-dominant trait, with variable penetrance. Differences in penetrance correlated with functional tests using E. coli complementation assays which showed that the p.V72I variant completely abolished, whereas the p.Q461E variant only mildly compromised bacterial growth.Created: 13 Apr 2022, 3:33 p.m. | Last Modified: 13 Apr 2022, 3:33 p.m.
Panel Version: 1.99
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Spastic paraplegia 13, autosomal dominant, OMIM:605280
Publications
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
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.
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: 25 Apr 2019, 1:22 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
Tag Q2_22_rating was removed from gene: HSPD1. Tag Q2_22_expert_review was removed from gene: HSPD1.
Gene: hspd1 has been classified as Amber List (Moderate Evidence).
Publications for gene: HSPD1 were set to 11898127
Tag Q2_22_rating tag was added to gene: HSPD1. Tag Q2_22_expert_review tag was added to gene: HSPD1.
Phenotypes for gene: HSPD1 were changed from Leukodystrophy, hypomyelinating, 4, autosomal recessive, 612233; Spastic paraplegia 13, autosomal dominant or pseudoautosomal, NOT imprinted, 605280 to Spastic paraplegia 13, autosomal dominant, OMIM:605280
Penetrance for gene HSPD1 was set from to None
Publications for gene: HSPD1 were set to
Source Yorkshire and North East GLH was added to HSPD1.
Source Expert Review Amber was added to HSPD1. Mode of inheritance for gene HSPD1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Leukodystrophy, hypomyelinating, 4, autosomal recessive, 612233; Spastic paraplegia 13, autosomal dominant or pseudoautosomal, NOT imprinted, 605280 for gene: HSPD1 Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Source NHS GMS was added to HSPD1.
gene: HSPD1 was added gene: HSPD1 was added to Hereditary spastic paraplegia - adult onset. Sources: London North GLH Mode of inheritance for gene: HSPD1 was set to