Hereditary neuropathy or pain disorder

Gene: CADM3

Green List (high evidence)

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

Created: 26 Sep 2024, 1:11 p.m. | Last Modified: 26 Sep 2024, 1:11 p.m.

Panel Version: 5.16

Comment on list classification: As reviewed by Ian Berry, there are now at least nine probands with peripheral neuropathy and with one of the two reported missense variants in heterozygous state. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 18 Apr 2024, 6:10 p.m. | Last Modified: 18 Apr 2024, 6:27 p.m.

Panel Version: 3.94

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

A second paper has been published with two further families - one de novo, and one with very significant segregation evidence, with the same variant.

There are four cases with neuromuscular disorders in GEL CVA who share one of the two published variants. Neither variant is in gnomAD, and neither is in a patient with an unrelated disorder in GEL.

In summary - there are now at least 9 probands with peripheral neuropathy who are heterozygous for one of the two published missense variants.

Created: 15 Apr 2024, 4:01 p.m. | Last Modified: 15 Apr 2024, 4:01 p.m.

Panel Version: 3.87

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• PMID: 38074074
• 33889941

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). To date only one paper reports three families with the same missense variant in CADM3. A separate report and/or another variant causing disease would help corroborate this association and so rating Amber for now with a 'watchlist' tag.

Created: 9 Dec 2022, 4:27 p.m. | Last Modified: 9 Dec 2022, 4:27 p.m.

Panel Version: 2.3

I don't know

Three families reported with the same missense variant in CADM3, p.Tyr172Cys (one family de novo), with functional work in mice to show reduced expression of the mutant protein in axons and abnormal axonal organization.
Sources: Literature

Created: 12 Jun 2021, 2:26 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Charcot-Marie-Tooth disease

Publications

• 33889941