Amelogenesis imperfecta

Gene: LAMC2

Amber List (moderate evidence)

LAMC2 (laminin subunit gamma 2)
EnsemblGeneIds (GRCh38): ENSG00000058085
EnsemblGeneIds (GRCh37): ENSG00000058085
OMIM: 150292, Gene2Phenotype
LAMC2 is in 4 panels

2 reviews

Claire Smith (University of Leeds)

Red List (low evidence)

Whilst biallelic mutations in LAMC2 are reported to cause Junctional Epidermolysis Bullosa (JEB) which may manifest amelogenesis imperfecta as part of its phenotype (when LAMA3 or LAMB3 genes are mutated), there are no obvious reports of patients with biallelic LAMC2 variants with enamel defects. Neither are heterozygous LAMC2 mutation carriers listed as having enamel defects. However, mutations in LAMA3 and LAMB3 have been shown to cause AI in some heterozygous carriers, so as LAMC2 variants are less frequently identified in cases of JEB, it may be that such carriers exist with AI but have not yet been identified. Reports on patients with LAMC2 variants lack detail as to whether there is enamel pathology or not, however it is a candidate gene due to it being part of a heterotrimeric protein with LAMA3 and LAMB3. Because of this, it is included in the Leeds AI Diagnostic Gene panel, contact Ruth Charlton, Leeds Teaching Hospitals.
Created: 18 Sep 2017, 3:36 p.m.

Mode of inheritance
Unknown

Phenotypes
Epidermolysis bullosa, junctional, Herlitz type, Epidermolysis bullosa, junctional, non Herlitz type

Publications

Mode of pathogenicity
Other

Rebecca Foulger (Genomics England curator)

Comment on mode of inheritance: Updated MOI to 'BOTH monoallelic and biallelic' after clinical agreement from Arianna Tucci to capture potential biallelic JEB patients with enamel defects, and heterozygous carriers with amelogenesis imperfecta.
Created: 31 Oct 2017, 2:25 p.m.
Comment on list classification: After internal discussion, updated the rating from Red to Amber. Although the evidence for being on the Leeds diagnostic panel is indirect (part of a complex with LAMA3 and LAMB3), LAMC2 is listed in the 'prior genetic testing' inclusion list.
Created: 19 Oct 2017, 7:51 a.m.
Comment on list classification: Kept rating as Red as there are currently insufficient cases of LAMC2 heterozygous carriers or LAMC2 biallelic JEB patients with enamel defects (see comment from expert Claire Smith). Added 'watchlist' tag to stay informed about additional cases.
Created: 18 Oct 2017, 11:35 a.m.
UKGTN gene dosier notes say that LAMC2 is not yet identified as a cause of AI in isolation, but is an excellent candidate.
Created: 8 Jun 2017, 10:09 a.m.
Comment on mode of inheritance: Monoallelic MOI taken from UKGTN gene dosier for 21-gene Amelogenesis imperfecta panel.
Created: 8 Jun 2017, 10:08 a.m.

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis Imperfecta
  • Epidermolysis bullosa, junctional, Herlitz type, 226700
  • Epidermolysis bullosa, junctional, non-Herlitz type, 226650
Tags
watchlist
OMIM
150292
Clinvar variants
Variants in LAMC2
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

31 Oct 2017, Gel status: 2

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for LAMC2 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

19 Oct 2017, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for LAMC2 were set to 26956061

19 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).

18 Oct 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).

18 Oct 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for LAMC2 were set to Amelogenesis Imperfecta; Epidermolysis bullosa, junctional, Herlitz type, 226700; Epidermolysis bullosa, junctional, non-Herlitz type, 226650

18 Oct 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).

8 Jun 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for LAMC2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

8 Jun 2017, Gel status: 1

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

LAMC2 was added to Amelogenesis Imperfectapanel. Source: UKGTN Model of inheritance for gene LAMC2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

8 Jun 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

LAMC2 was added to Amelogenesis Imperfectapanel. Sources: Eligibility statement prior genetic testing

8 Jun 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

LAMC2 was created by rfoulger