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| Amelogenesis imperfecta v4.5 | AIRE |
Claire Smith changed review comment from: It is well reported that 70-90% of patients with APS-1 (# 240300) have enamel formation defects of various severity. These patients have mutations in the AIRE gene (see PMID 19393987;27253668). Paper in 2023 (PMID 37993717) reported that there is autoreactivity against enamel antigens in Aire-/- mouse models and that this is also seen in (against ameloblast-specific proteins) in patients with APS-1. The authors looked at 17 patients total and saw autoantibodies in all to enamel specific proteins, see figure 1F. Immunofluorescence microscopy analysis demonstrated largely overlapping signals from APS-1 serum with that from AMELX- and LAMB3-specific antibodies. Moreover, ELISA analyses revealed that both paediatric and adult patients with APS-1 have IgA autoantibodies against several ameloblast antigens, including LAMB3, FAM20A, ENAM and AMELX, or IgG1 autoantibodies against ACPT. Overall, all patients tested with APS-1 developed autoantibodies against at least one of the five major ameloblast antigens, with distinct reactivity clusters. Furthermore, patients with severe enamel defects had significantly higher levels of autoantibody reactivity against all of the tested enamel antigens compared with those with mild enamel defects or age-matched healthy control individuals. Moreover, canines, which have the longest mineralization period (around 6.5 years), had the most pronounced enamel defects, in comparison to incisors or first molars, of which the mineralization period is significantly shorter (around 4.5 and 3 years, respectively), suggesting that the longer the mineralization period, the higher the chance for enamel-specific autoantibodies to interfere and cause damage in enamel formation. This is a really interesting mechanism of disease, whereby mutations in AIRE can cause the development of self antigens against the proteins that make enamel, which leads to amelogenesis imperfecta. Note that the paper does not specify whether patients were mono or biallelic carriers of the AIRE variants, note that OMIM records that both mono and balletic variants can cause APS-1. Note that the authors also looked at patients with coeliac disease and found similar autoantibodies against enamel proteins. Sources: Literature; to: It is well reported that 70-90% of patients with APS-1 (# 240300) have enamel formation defects of various severity. These patients have mutations in the AIRE gene (see PMID 19393987;27253668). Paper in 2023 (PMID 37993717) reported that there is autoreactivity against enamel antigens in Aire-/- mouse models and that this is also seen in (against ameloblast-specific proteins) in patients with APS-1. The authors looked at 17 patients total and saw autoantibodies in all to enamel specific proteins, see figure 1F. Immunofluorescence microscopy analysis demonstrated largely overlapping signals from APS-1 serum with that from AMELX- and LAMB3-specific antibodies. Moreover, ELISA analyses revealed that both paediatric and adult patients with APS-1 have IgA autoantibodies against several ameloblast antigens, including LAMB3, FAM20A, ENAM and AMELX, or IgG1 autoantibodies against ACPT. Overall, all patients tested with APS-1 developed autoantibodies against at least one of the five major ameloblast antigens, with distinct reactivity clusters. Furthermore, patients with severe enamel defects had significantly higher levels of autoantibody reactivity against all of the tested enamel antigens compared with those with mild enamel defects or age-matched healthy control individuals. Moreover, canines, which have the longest mineralization period (around 6.5 years), had the most pronounced enamel defects, in comparison to incisors or first molars, of which the mineralization period is significantly shorter (around 4.5 and 3 years, respectively), suggesting that the longer the mineralization period, the higher the chance for enamel-specific autoantibodies to interfere and cause damage in enamel formation. This is a really interesting mechanism of disease, whereby mutations in AIRE can cause the development of self antigens against the proteins that make enamel, which leads to amelogenesis imperfecta. Note that the paper does not specify whether patients were mono or biallelic carriers of the AIRE variants, note that OMIM records that both mono and balletic variants can cause APS-1. Note that the authors also looked at patients with coeliac disease and found similar autoantibodies against enamel proteins. Sources: Literature Edit: I didn't add Amelogenesis imperfecta to the phenotype list. Can you please add this! I can't seem to add it in retrospect! |
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| Amelogenesis imperfecta v4.5 | AIRE |
Claire Smith gene: AIRE was added gene: AIRE was added to Amelogenesis imperfecta. Sources: Literature Mode of inheritance for gene: AIRE was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: AIRE were set to PMID: 37993717; 19393987; 27253668 Phenotypes for gene: AIRE were set to Addison disease; hypoparathyroidism; chronic mucocutaneous candidiasis Penetrance for gene: AIRE were set to unknown Review for gene: AIRE was set to GREEN Added comment: It is well reported that 70-90% of patients with APS-1 (# 240300) have enamel formation defects of various severity. These patients have mutations in the AIRE gene (see PMID 19393987;27253668). Paper in 2023 (PMID 37993717) reported that there is autoreactivity against enamel antigens in Aire-/- mouse models and that this is also seen in (against ameloblast-specific proteins) in patients with APS-1. The authors looked at 17 patients total and saw autoantibodies in all to enamel specific proteins, see figure 1F. Immunofluorescence microscopy analysis demonstrated largely overlapping signals from APS-1 serum with that from AMELX- and LAMB3-specific antibodies. Moreover, ELISA analyses revealed that both paediatric and adult patients with APS-1 have IgA autoantibodies against several ameloblast antigens, including LAMB3, FAM20A, ENAM and AMELX, or IgG1 autoantibodies against ACPT. Overall, all patients tested with APS-1 developed autoantibodies against at least one of the five major ameloblast antigens, with distinct reactivity clusters. Furthermore, patients with severe enamel defects had significantly higher levels of autoantibody reactivity against all of the tested enamel antigens compared with those with mild enamel defects or age-matched healthy control individuals. Moreover, canines, which have the longest mineralization period (around 6.5 years), had the most pronounced enamel defects, in comparison to incisors or first molars, of which the mineralization period is significantly shorter (around 4.5 and 3 years, respectively), suggesting that the longer the mineralization period, the higher the chance for enamel-specific autoantibodies to interfere and cause damage in enamel formation. This is a really interesting mechanism of disease, whereby mutations in AIRE can cause the development of self antigens against the proteins that make enamel, which leads to amelogenesis imperfecta. Note that the paper does not specify whether patients were mono or biallelic carriers of the AIRE variants, note that OMIM records that both mono and balletic variants can cause APS-1. Note that the authors also looked at patients with coeliac disease and found similar autoantibodies against enamel proteins. Sources: Literature |
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| Amelogenesis imperfecta | LAMB3 | Rebecca Foulger marked LAMB3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Amelogenesis imperfecta | LAMB3 | Rebecca Foulger marked LAMB3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Amelogenesis imperfecta | LAMB3 | Rebecca Foulger classified LAMB3 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Amelogenesis imperfecta | LAMB3 | Rebecca Foulger commented on LAMB3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Amelogenesis imperfecta | LAMB3 | Claire Smith reviewed LAMB3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||