Adult onset neurodegenerative disorder

Gene: SS18L1

This gene is not currently associated with a disease phenotype in OMIM, but checked PMID:24360741 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tag.

Created: 16 Oct 2023, 7:33 p.m. | Last Modified: 16 Oct 2023, 7:33 p.m.

Panel Version: 4.37

Green List (high evidence)

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

Created: 10 Oct 2023, 4:47 p.m. | Last Modified: 10 Oct 2023, 4:55 p.m.

Panel Version: 4.37

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

Created: 11 Apr 2023, 4:33 p.m. | Last Modified: 11 Apr 2023, 4:33 p.m.

Panel Version: 4.10

Not associated with a phenotype in OMIM, Gen2Phen or MONDO. Three monoallelic variants have been reported in three unrelated cases of Amyotrophic lateral sclerosis (ALS). Expression of rs587777632 in mouse primary cortical neurons, inhibited stimulation-induced dendrite outgrowth and decreased complexity of dendritic arbors in a dominant-negative manner, while rs587777633 in mouse primary motor neurons, blocked depolarization-induced dendrite outgrowth and increased in dendritic arbor complexity (PMID: 23708140). Using SS18L1 knockout and SS18L1 p.Q394X knock-in mice, Cheng et al (PMID: 30976389), were able to observe compromised motor coordination in the mice and furthermore, elevated inflammatory responses were apparent; suggesting that there maybe an elevated inflammatory response within patients.

Created: 11 Apr 2023, 4:32 p.m. | Last Modified: 11 Apr 2023, 4:32 p.m.

Panel Version: 4.9

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Green List (high evidence)

>3 cases with heterozygous variants (de novo status confirmed or expected), and supporting functional evidence.

Created: 28 Sep 2020, 4:13 a.m. | Last Modified: 28 Sep 2020, 4:13 a.m.

Panel Version: 2.16

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Amyotrophic lateral sclerosis

Publications

• 25888396
• 24360741
• 23708140
• 30976389

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

I don't know

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 Amber

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

Panel Version: 1.106

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

Green List (high evidence)

Two families and two sporadic cases with at least one de novo variant identified.

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

Panel Version: 1.72

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Amyotrophic lateral sclerosis, 105400

Publications

• 23708140
• 24360741