Hereditary neuropathy or pain disorder
Gene: CADM3
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
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
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
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: LiteratureCreated: 12 Jun 2021, 2:26 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Charcot-Marie-Tooth disease
Publications
Tag Q2_24_promote_green tag was added to gene: CADM3. Tag Q2_24_NHS_review tag was added to gene: CADM3.
Gene: cadm3 has been classified as Amber List (Moderate Evidence).
Publications for gene: CADM3 were set to 33889941
Gene: cadm3 has been classified as Amber List (Moderate Evidence).
Tag watchlist tag was added to gene: CADM3.
Phenotypes for gene: CADM3 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, axonal, type 2FF, OMIM:619519
gene: CADM3 was added gene: CADM3 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: Literature Mode of inheritance for gene: CADM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CADM3 were set to 33889941 Phenotypes for gene: CADM3 were set to Charcot-Marie-Tooth disease Review for gene: CADM3 was set to AMBER