Amelogenesis imperfecta

Gene: AMTN

Amber List (moderate evidence)

AMTN (amelotin)
EnsemblGeneIds (GRCh38): ENSG00000187689
EnsemblGeneIds (GRCh37): ENSG00000187689
OMIM: 610912, Gene2Phenotype
AMTN is in 1 panel

2 reviews

Claire Smith (University of Leeds)

Red List (low evidence)

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/AMTN
3 Aug 2017, 2:01 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Amelogenesis imperfecta, hypomaturation type

Publications

Rebecca Foulger (Genomics England curator)

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".
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.
16 Aug 2017, 2:23 p.m.
Comment when marking as ready: Marked as Ready: August 16th 2017.
16 Aug 2017, 2:22 p.m.
Comment on mode of inheritance: Updated MOI to 'NOT imprinted' to match reviewer's suggestion.
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.
12 Jun 2017, 9:12 a.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Amelogenesis imperfecta
  • dominant hypomineralised AI
  • Amelogenesis imperfecta, hypomaturation type
  • ?Amelogenesis imperfecta, type IIIB, 617607
Tags
deletions watchlist
OMIM
610912
Clinvar variants
Variants in AMTN
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

2 Feb 2018, Gel status: 2

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

This panel has been promoted after review by Claire Smith (Leeds) and further personal consultation with Dr Smith

24 Oct 2017, Gel status: 2

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Amber List (Moderate Evidence).

16 Aug 2017, Gel status: 1

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Red List (Low Evidence).

16 Aug 2017, Gel status: 1

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Red List (Low Evidence).

16 Aug 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for AMTN were set to Amelogenesis imperfecta; dominant hypomineralised AI; Amelogenesis imperfecta, hypomaturation type; ?Amelogenesis imperfecta, type IIIB, 617607

16 Aug 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for AMTN was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

16 Aug 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for AMTN were set to Amelogenesis imperfecta; dominant hypomineralised AI; Amelogenesis imperfecta, hypomaturation type

12 Jun 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

AMTN was added to Amelogenesis Imperfectapanel. Sources: Literature

12 Jun 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

AMTN was created by rfoulger