Arthrogryposis

Gene: LGI3

Green List (high evidence)

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

Created: 26 Sep 2024, 12:24 p.m. | Last Modified: 26 Sep 2024, 12:24 p.m.

Panel Version: 7.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.

Created: 30 Jan 2024, 10:55 a.m. | Last Modified: 30 Jan 2024, 11:20 a.m.

Panel Version: 5.22

PMID:35948005 reported sixteen individuals from eight unrelated families with loss-of-function (LoF) bi-allelic variants in LGI3. All of them exhibited a potentially clinically recognizable peripheral nerve hyperexcitability syndrome (PNHS) trait characterized by global developmental delay, intellectual disability, distal deformities with diminished reflexes, visible facial myokymia, and distinctive electromyographic features suggestive of motor nerve instability.

Distal deformities included knee, hip, and ankle contractures (4/14); contractures/deformities of fingers and feet (6/14); and other uncharacterized deformities (4/14). All sixteen patients had global developmental delay and all thirteen tested patients had mild or moderate intellectual disability.

Lgi3-null mice showed reduced and mis-localized Kv1 channel complexes in myelinated peripheral axons.

This gene has been associated with relevant phenotypes in OMIM (MIM #620007), but not yet in Gene2Phenotype.
Sources: Literature

Created: 30 Jan 2024, 10:54 a.m. | Last Modified: 30 Jan 2024, 10:58 a.m.

Panel Version: 5.22

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects, OMIM:620007

Publications

• 35948005