Adult onset hereditary spastic paraplegia

Gene: SERAC1

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 14 Mar 2022, 1:19 p.m. | Last Modified: 14 Mar 2022, 1:19 p.m.

Panel Version: 1.95

Review of literature did not reveal any adult onset cases - disorder presents at birth and severe spasticity becomes apparent, typically with disease progression, during the infantile or childhood period.

The 'Q3_21_phenotype' tag has been added to highlight that this is a childhood onset condition. Leaving the rating as Green, but with a recommendation for review at the next GMS panel update. This gene is already Green on the 'Hereditary spastic paraplegia - childhood onset v.2.18' panel.

Created: 20 Aug 2021, 2:11 p.m. | Last Modified: 20 Aug 2021, 2:11 p.m.

Panel Version: 1.47

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, OMIM:614739

Publications

• 16527507
• 22683713
• 23918762
• 27186703
• 28778788
• 29205472

Red List (low evidence)

Childhood onset.

Created: 22 Sep 2020, 5:17 a.m. | Last Modified: 22 Sep 2020, 5:17 a.m.

Panel Version: 1.7

I don't know

Childhood onset. No reports of adult onset.

Created: 10 May 2019, 9:21 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 29205472
• 22683713
• 16527507
• 28482397
• 28778788
• 27186703
• 27604308

I don't know

Green gene with Amber 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, 4:14 p.m.

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.

Green List (high evidence)

several publications were spasticity is mentioned in pt phenotype. PubMed: 28916646 6 members of a large consanguineous Iraqi family with a mild variant of 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome. patients also presented with juvenile-onset progressive spastic paraplegia and mild cognitive impairment, although none had deafness. The findings expanded the phenotypic spectrum associated with SERAC1 mutations.. Victoria: GREEN

Created: 25 Apr 2019, 1:22 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, Autosomal dominant, 614739; MEGDEL syndrome; 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome; MEGDHEL syndrome