White matter disorders and cerebral calcification - narrow panel

Gene: DEGS1

Green List (high evidence)

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

Created: 30 Jan 2023, 4:26 p.m. | Last Modified: 30 Jan 2023, 4:26 p.m.

Panel Version: 2.9

Green List (high evidence)

Comment on list classification: Promoting from grey to amber, but with a recommendation for green rating at the next GMS review. >3 cases reported with a plausible disease causing variant in DEGS1. Presentation is in young children.

Created: 27 Apr 2021, 7:30 p.m. | Last Modified: 27 Apr 2021, 7:30 p.m.

Panel Version: 1.50

Associated with Leukodystrophy, hypomyelinating, 18 #618404 (AR) in OMIM.

PMID: 30620338 - Karsai et al 2019 - identified a missense variant in DEGS1 in a patient with a sphingolipid disorder with leukodystrophy and hypomyelination of the peripheral nervous system. The consanguineous parents were of Turkish origin. Motor developmental delay was first noted at 6 months.

PMID: 30620337 - Pant et al 2019 - report 19 individuals with hypomyelinating leukodystrophies from 13 unrelated families and homozygous or compound heterozygous variants identified in DEGS1 gene. The average age of onset was 5.6 months.

PMID: 31186544 - Dolgin et al 2019 - report a large inbred consanguineous Arab Israeli family in which 4 individuals presented with a complex neurological disorder with mild to severe intellectual disability, spastic quadriplegia, scoliosis and epilepsy. Brain MRI findings were suggestive of leukodystrophy. WES identified a missense variant in DEGS1 that segregated with the disorder. All presented with initial symptoms in early childhood (<2 years old).

Created: 27 Apr 2021, 7:28 p.m. | Last Modified: 27 Apr 2021, 7:28 p.m.

Panel Version: 1.47

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 18, OMIM:618404

Publications

• 30620338
• 30620337
• 31186544

Green List (high evidence)

20 individuals from 14 unrelated families. Hypomyelinating leukodystorphy is the prominent feature of this condition.
Sources: Expert list

Created: 15 Sep 2020, 10:10 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 18, MIM#618404

Publications

• 30620338
• 30620337

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