Adult onset neurodegenerative disorder

Gene: SPG21

Green List (high evidence)

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

Created: 10 Oct 2023, 4:47 p.m. | Last Modified: 10 Oct 2023, 4:47 p.m.

Panel Version: 4.37

Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least three variants have been reported in three unrelated cases (PMIDs: 14564668, 24451228, 28752238), together with a supportive mouse model (PMID: 26978163).

Created: 6 Apr 2023, 4:13 p.m. | Last Modified: 6 Apr 2023, 4:13 p.m.

Panel Version: 4.3

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 6 Apr 2023, 4:04 p.m. | Last Modified: 6 Apr 2023, 4:04 p.m.

Panel Version: 4.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Founder variant in Amish, two additional families and a mouse model. Progressive adult-onset disorder.

Created: 25 Sep 2020, 2:57 a.m. | Last Modified: 25 Sep 2020, 2:57 a.m.

Panel Version: 2.16

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mast syndrome, MIM# 248900

Publications

• 14564668
• 24451228
• 28752238
• 26978163

I don't know

Gene now called ACP33 in OMIM. Mast syndrome is an autosomal recessive complicated form of hereditary spastic paraplegia in which progressive spastic paraparesis is associated in more advanced cases with cognitive decline, dementia, and other neurologic abnormalities. Symptom onset usually occurs in adulthood, and the disorder is progressive with variable severity. Only 3 variants listed in HGMDpro, one is a missense with no functional studies - amber?

Created: 2 Sep 2019, 4:06 p.m. | Last Modified: 2 Sep 2019, 4:06 p.m.

Panel Version: 1.99

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic Paraplegia, Recessive

Green List (high evidence)

No additional patient identified using Sheffield panel.

Created: 23 Jul 2019, 3:35 p.m. | Last Modified: 23 Jul 2019, 3:35 p.m.

Panel Version: 1.72

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic Paraplegia, Recessive

Publications

• 14564668
• 28752238
• 24451228

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

Red List (low evidence)

As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red

Created: 20 Sep 2019, 4:19 p.m. | Last Modified: 20 Sep 2019, 4:19 p.m.

Panel Version: 1.106

Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group. All the green and amber, except for the genes with triplet repeats, were reviewed.

Created: 2 Sep 2019, 4:46 p.m. | Last Modified: 2 Sep 2019, 4:46 p.m.

Panel Version: 1.101

Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.

Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.

Panel Version: 1.74

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

Created: 23 Apr 2019, 5:35 p.m.

Green List (high evidence)