Amelogenesis imperfecta
Gene: AMTN
Only one AMTN mutation has been associated with AI to date; an in-frame deletion spanning exons 3 to 6. The family exhibited hypomineralised AI with autosomal dominant inheritance. Whilst it is likely that this was the cause of the phenotype due to the phenotypes observed in mouse models of Amtn function and through experimental evidence of the role of AMTN in enamel formation, this was not proven absolutely. The discovery of additional families with AMTN variants will help to confirm this candidate gene. See AMTN LOVD: http://dna2.leeds.ac.uk/LOVD/genes/AMTNCreated: 3 Aug 2017, 2:01 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Amelogenesis imperfecta, hypomaturation type
Publications
Comment on list classification: Updated rating from Red to Amber, and added 'watchlist' and 'deletion' tags based on updated email correspondence from Claire Smith (October 23rd 2017): "I really think AMTN is causative but only for particular mutations. I have sequenced additional family members since my publication and I am convinced than the heterozygous deletion of exons 3-6 is causative for this AD family. I have never identified a missense in amtn, but my belief is that AR inheritance might result for LOF mutations, but a mild phenotype only".Created: 24 Oct 2017, 8:21 a.m.
Comment on list classification: Kept rating as red: Only 1 (Costa Rican) case so far and lack of evidence is supported by Red expert review.Created: 16 Aug 2017, 2:23 p.m.
Comment when marking as ready: Marked as Ready: August 16th 2017.Created: 16 Aug 2017, 2:22 p.m.
Comment on mode of inheritance: Updated MOI to 'NOT imprinted' to match reviewer's suggestion.Created: 16 Aug 2017, 2:21 p.m.
PMID:27412008 use WES to identify an 8,678 bp heterozygous genomic deletion encompassing exons 3-6 of AMTN in a Costa Rican family segregating dominant hypomineralised AI. The deletion corresponds to an in-frame deletion of 92 amino acids, shortening the protein from 209 to 117 residues.Created: 12 Jun 2017, 9:12 a.m.
This panel has been promoted after review by Claire Smith (Leeds) and further personal consultation with Dr Smith
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
Phenotypes for AMTN were set to Amelogenesis imperfecta; dominant hypomineralised AI; Amelogenesis imperfecta, hypomaturation type; ?Amelogenesis imperfecta, type IIIB, 617607
Mode of inheritance for AMTN was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for AMTN were set to Amelogenesis imperfecta; dominant hypomineralised AI; Amelogenesis imperfecta, hypomaturation type
AMTN was added to Amelogenesis Imperfectapanel. Sources: Literature
AMTN was created by rfoulger