Amelogenesis imperfecta

Gene: FAM83H

Green List (high evidence)

FAM83H (family with sequence similarity 83 member H)
EnsemblGeneIds (GRCh38): ENSG00000180921
EnsemblGeneIds (GRCh37): ENSG00000180921
OMIM: 611927, Gene2Phenotype
FAM83H is in 1 panel

2 reviews

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Marked as ready: October 18th 2017.
18 Oct 2017, 11:39 a.m.
Comment on mode of pathogenicity: Expert reviewer Claire Smith notes that all but 2 mutations identified so far are nonsense or frameshift variants in the last exon leading to premature translation termination. And the truncated products may cause AI through a dominant gain of function effect.
16 Aug 2017, 9:17 a.m.
Comment on list classification: Updated rating from Amber to Green: Green expert review and on the Leeds diagnostic panel. Although no disease yet curated in DD-G2P, there are plenty of cases to support causation: As Claire Smith reports, FAM83H is the gene most commonly identified as a cause for AI to date.
16 Aug 2017, 9:16 a.m.
Comment on mode of inheritance: Updated MOI to 'NOT imprinted' to match review by Claire Smith.
16 Aug 2017, 8:49 a.m.

Claire Smith (University of Leeds)

Green List (high evidence)

Currently on the Leeds AI diagnostic panel (Contact: Ruth Charlton). Gene most commonly identified as a cause of AI in reports to date - accounts for over 19% of cases. Associated with hypocalcified AI. All of the mutations identified so far have been located in the final, largest exon and all but two are nonsense or frameshift variants predicted to lead to premature translation termination. As terminating mutations in the last exon are generally not subject to NMD, the truncated products may cause AI through a dominant gain of function effect.

All of the twenty-seven FAM83H mutations identified reside within the first 1343 bp of the final exon (up to Glu694) with the final 1460 bp devoid of known mutations, suggesting that this region may not be critical to FAM83H function. In addition, some degree of phenotypic variation has been reported in patients, with mutations predicted to produce longer truncation products having a milder phenotype confined to just the cervical areas of the teeth . See FAM83H LOVD: http://dna2.leeds.ac.uk/LOVD/genes/FAM83H
2 Aug 2017, 3:11 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Amelogenesis imperfecta, type III 130900

Publications

Mode of pathogenicity
Other

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis imperfecta, type III, 130900
  • Amelogenesis Imperfecta, Type III, 130900
  • Hypocalcified AI
OMIM
611927
Clinvar variants
Variants in FAM83H
Penetrance
Complete
Publications
Mode of Pathogenicity
Other - please provide details in the comments
Panels with this gene

History Filter Activity

2 Feb 2018, Gel status: 3

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

18 Oct 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

16 Aug 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

16 Aug 2017, Gel status: 4

Set mode of pathogenicity

Rebecca Foulger (Genomics England curator)

Mode of pathogenicity for FAM83H was changed to Other - please provide details in the comments

16 Aug 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

16 Aug 2017, Gel status: 2

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for FAM83H was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

16 Aug 2017, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for FAM83H were set to Amelogenesis imperfecta, type III, 130900; Amelogenesis Imperfecta, Type III, 130900; Hypocalcified AI

16 Aug 2017, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for FAM83H were set to 20160442; 19407157; 18484629; 21702852; 19407157; 22414746; 18252228; 21597265; 19828885; 19825039; 19220331; 26788537; 21118793; 26502894; 26171361; 26481691; 26142250

8 Jun 2017, Gel status: 2

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

FAM83H was added to Amelogenesis Imperfectapanel. Source: UKGTN Model of inheritance for gene FAM83H was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

8 Jun 2017, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

FAM83H was added to Amelogenesis Imperfectapanel. Source: Radboud University Medical Center, Nijmegen

8 Jun 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

FAM83H was created by rfoulger

8 Jun 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

FAM83H was added to Amelogenesis Imperfectapanel. Sources: Eligibility statement prior genetic testing