Hereditary neuropathy
Gene: JAG1Comment on list classification: New gene added by Alexander Rossor (UCL). Sullivan et al., 2020 (PMID:32065591) report two unrelated families with segregation, presenting vocal fold paresis. Knock in mouse model showed slight but nonsignificant reduction in compound muscle action potential and morphological assessments of the recurrent laryngeal nerve were normal. Mice did however display an increased frequency of axons with focally folded myelin. Notably, variants in JAG1 are associated with several phenotypes that have not included neuropathy and there was no history of cardiac, kidney, or liver disease in affected individuals in either of the two families discussed here (possibly different mechanisms of pathogenesis but further investigation may be warranted).
At this point there is not enough evidence to add this gene as diagnostic-grade; however, additional cases would corroborate this gene-disease association - rating Amber with 'watchlist' tag.Created: 6 Sep 2021, 11:13 a.m. | Last Modified: 6 Sep 2021, 11:13 a.m.
Panel Version: 1.407
Two unrelated families with segregation but no definite neuropathy in knock in mouse model
Sources: Expert listCreated: 8 Mar 2021, 10:46 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Vocal cord palsy
Publications
Mode of pathogenicity
Other
Tag watchlist tag was added to gene: JAG1.
Phenotypes for gene: JAG1 were changed from Vocal cord palsy to Vocal cord palsy; Peripheral neuropathy
Gene: jag1 has been classified as Amber List (Moderate Evidence).
gene: JAG1 was added gene: JAG1 was added to Hereditary neuropathy. Sources: Expert list Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: JAG1 were set to PMID: 32065591 Phenotypes for gene: JAG1 were set to Vocal cord palsy Penetrance for gene: JAG1 were set to Complete Mode of pathogenicity for gene: JAG1 was set to Other Review for gene: JAG1 was set to AMBER