Amelogenesis imperfecta

Gene: COL17A1

Green List (high evidence)

COL17A1 (collagen type XVII alpha 1 chain)
EnsemblGeneIds (GRCh38): ENSG00000065618
EnsemblGeneIds (GRCh37): ENSG00000065618
OMIM: 113811, Gene2Phenotype
COL17A1 is in 4 panels

2 reviews

Claire Smith (University of Leeds)

Green List (high evidence)

Included in the Leeds AI Diagnostic panel by Yorkshire Regional Genetics.

Heterozygous COL17A1 mutation carriers with an AI phenotype harbour glycine substitutions, as well as nonsense, frameshift and splicing mutations (McGrath et al., 1996; Murrell et al., 2007). The nonsense and frameshift mutations identified would be expected to lead to NMD, suggesting that the cause of the phenotype is haploinsufficiency. The glycine substitutions are predicted to disrupt an extracellular collagenous triple helix, potentially affecting both the susceptibility of the protein to degradation and its secretion (McGrath et al., 1996). At least 11 AI-causing variants have been identified according to the Leeds AI database (http://dna2.leeds.ac.uk/LOVD/genes).
Created: 17 Nov 2017, 9:40 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Amelogenesis imperfecta; Epidermolysis bullosa (if biallelic)

Publications

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Marked as ready: October 31st 2017.
Created: 31 Oct 2017, 2:21 p.m.
Comment on mode of inheritance: Kept MOI as 'BOTH monoallelic and biallelic' after clinical agreement from Arianna Tucci to capture both biallelic JEB patients with enamel defects, and heterozygous carriers with amelogenesis imperfecta.
Created: 31 Oct 2017, 2:21 p.m.
Comment on list classification: Updated rating from Red to Green, awaiting external review. Sufficient (>3) independent cases to support causation of enamel phenotype. Plus COL17A1 is included in the 'prior genetic testing' inclusion list, and is included on the UKGTN 21-gene panel for AI.
Created: 19 Oct 2017, 8:59 a.m.
PMID:16820943 (Nakamura et al., 2006) conducted COL17A1 mutational analysis in 3 patients from 2 unrelated nH-JEB families: 1 nH-JEB patient showed no COL17A1 expression and was a compound heterozygote for premature termination mutations 1285delA and Q1387X. Reduced COL17A1 expression was found in a 2nd nH-JEB patient homozygous for the premature termination mutation 4335delC. The authors didn't detect any pathogenic COL17A1 defects in AI patients.
Created: 19 Oct 2017, 8:57 a.m.
Comment on mode of inheritance: MOI listed as autosomal dominant in the UKGTN gene dosier for AI. In the biallelic state, COL17A1 variants cause junctional non-Herlitz-type epidermolysis bullosa (MIM:226650), with associated dental enamel defects. However, cases of isolated ADAI in heterozygous carriers have been reported.
Created: 19 Oct 2017, 8:52 a.m.
PMID:8669466 (1996) report a patient with a form of JEB with skin fragility and dental anomalies who is a COL17A1 compound heterozygote for p.(Gly627Val) plus an internal duplication. The 2 offspring of the patient show no evidence of skin fragility but have marked dental abnormalities with enamel hypoplasia and pitting. The offspring have inherited the p.(Gly627Val) substitution variant only (i.e. are heterozygotes).
Created: 19 Oct 2017, 8:44 a.m.
PMID:26502894 (2016) perform a large scale sequencing screen for orodental genetic disorders. They find 4 independent patients segregating pathogenic variants (including 3 novel) in COL17A1. Patient V2.82 had 2 variants; a maternally inherited novel COL17A1 splice mutation (c.1141+1G>A) and a novel LAMA3 frameshift-inducing deletion (p.I2159Mfs*46) that is absent in her affected mother. Her phenotype was more severe than her mother, suggesting digenic inheritance in this patient- have added 'monogenic-polygenic' tag to capture this patient.
Created: 19 Oct 2017, 8:29 a.m.
PMID:27558265 (2016) identified a large consanguineous Moroccan family segregating different clinical subtypes of hypoplastic and hypomineralized AI. The authors identified a novel heterozygous nonsense mutation in COL17A1 (c.1873C>T, p.R625*) segregating with hypoplastic AI.
Created: 8 Jun 2017, 12:31 p.m.

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Epidermolysis bullosa, junctional, non-Herlitz type, 226650 (includes enamel pitting)
  • Amelogenesis Imperfecta
  • non-Herlitz junctional epidermolysis bullosa (nH-JEB) and amelogenesis imperfecta
  • hypoplastic amelogenesis imperfecta
Tags
monogenic-polygenic
OMIM
113811
Clinvar variants
Variants in COL17A1
Penetrance
Complete
Publications
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

31 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).

31 Oct 2017, Gel status: 4

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for COL17A1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

19 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).

19 Oct 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for COL17A1 were set to 16820943; 27558265; 26502894; 8669466

19 Oct 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for COL17A1 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

19 Oct 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for COL17A1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

19 Oct 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for COL17A1 were set to Epidermolysis bullosa, junctional, non-Herlitz type, 226650 (includes enamel pitting); Amelogenesis Imperfecta; non-Herlitz junctional epidermolysis bullosa (nH-JEB) and amelogenesis imperfecta; hypoplastic amelogenesis imperfecta

19 Oct 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for COL17A1 were set to Epidermolysis bullosa, junctional, non-Herlitz type, 226650 (includes enamel pitting) Amelogenesis Imperfecta; non-Herlitz junctional epidermolysis bullosa (nH-JEB) and amelogenesis imperfecta; hypoplastic amelogenesis imperfecta

19 Oct 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for COL17A1 were set to 16820943; 27558265; 26502894

8 Jun 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for COL17A1 were set to Amelogenesis Imperfecta; non-Herlitz junctional epidermolysis bullosa (nH-JEB) and amelogenesis imperfecta; hypoplastic amelogenesis imperfecta

8 Jun 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for COL17A1 were set to Amelogenesis Imperfecta; non-Herlitz junctional epidermolysis bullosa (nH-JEB) and amelogenesis imperfecta; hypoplastic amelogenesis imperfecta; hypomineralized amelogenesis imperfecta

8 Jun 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for COL17A1 were set to 16820943; 27558265

8 Jun 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for COL17A1 were set to Amelogenesis Imperfecta

8 Jun 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for COL17A1 were set to 16820943

8 Jun 2017, Gel status: 1

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

COL17A1 was added to Amelogenesis Imperfectapanel. Source: UKGTN Model of inheritance for gene COL17A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

8 Jun 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

COL17A1 was added to Amelogenesis Imperfectapanel. Sources: Eligibility statement prior genetic testing

8 Jun 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

COL17A1 was created by rfoulger