Amelogenesis imperfecta

Gene: LAMA3

Green List (high evidence)

LAMA3 (laminin subunit alpha 3)
EnsemblGeneIds (GRCh38): ENSG00000053747
EnsemblGeneIds (GRCh37): ENSG00000053747
OMIM: 600805, Gene2Phenotype
LAMA3 is in 4 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Marked as ready: October 31st 2017.
Created: 31 Oct 2017, 2:27 p.m.
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, 2:27 p.m.
Comment when marking as ready: Marked as Ready: 19th September 2017.
Created: 19 Sep 2017, 6:53 a.m.
Comment on list classification: Updated rating from Red to Green after clinical advice from Helen Brittain: Green expert rating plus 3 cases of heterozygotes with enamel problems.
Created: 19 Sep 2017, 6:52 a.m.
Comment on mode of inheritance: Kept rating as monoallelic after clinical advice from Helen Brittain: heterozygotes display enamel abnormalities, and biallelic JEB patients (which can be accompanied with enamel defects) would instead be assigned the 'Epidermolysis bullosa' panel.
Created: 19 Sep 2017, 6:51 a.m.
PMID:22434185 reports enamel defects in carriers of a LAMA3 variant. The proband was compound heterozygote for LAMA3 variants (c.4484C>T and c.488delG) and diagnosed with JEB-nH (Junctional epidermolysis bullosa, non-Herlitz). Her mother and brother who showed heterozygosity for c.488delG, and had enamel defects.
Created: 17 Aug 2017, 7:11 a.m.
PMID:27827380 (2016) report 2 null mutations (Arg793Ter and splice-site c.4684+1G>A mutation) in heterozygous carriers showing enamel pitting. Both parents had offspring affected with JEB and subtle enamel pitting.
Created: 16 Aug 2017, 3:41 p.m.
Added monogenic-polygenic tag since PMID:26502894 predict that the AI phenotype of patient V2.82 is likely to be digenic with COL17A1.
Created: 16 Aug 2017, 3:36 p.m.
PMID:26502894 (Prasad et al., 2016) describe patient V2.82 with hypoplastic AI and 2 unlinked mutations, one maternally-inherited COL17A1 splice mutation and a novel LAMA3 frameshift-inducing deletion (p.I2159Mfs*46) that is absent in her mother. The unaffected father was unavailable for testing. Patient's V2.82 enamel phenotype is more severe than her mother's suggesting digenic inheritance in this individual.
Created: 16 Aug 2017, 3:34 p.m.
Not currently associated with AI on OMIM. UKGTN gene dosier notes say that the research group is currently aware of at least 1 case of AI in isolation, and unclear if LAMA3 is rare cause of AI.
Created: 8 Jun 2017, 10:07 a.m.
Comment on mode of inheritance: Monoallelic MOI taken from UKGTN gene dosier for 21-gene Amelogenesis imperfecta panel.
Created: 8 Jun 2017, 10:06 a.m.

Claire Smith (University of Leeds)

Green List (high evidence)

Currently on the Leeds AI diagnostic panel (Contact: Ruth Charlton). LAMA3 variants that cause AI in heterozygous carriers, also cause JEB in biallelic individuals. See LAMA3 LOVD: http://dna2.leeds.ac.uk/LOVD/genes/LAMA3
Created: 3 Aug 2017, 2:14 p.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Amelogenesis imperfecta, hypoplastic type; Epidermolysis bullosa, generalized atrophic benign 226650; Epidermolysis bullosa, junctional, Herlitz type 226700; Laryngoonychocutaneous syndrome 245660

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis imperfecta, hypoplastic type
  • Epidermolysis bullosa, generalized atrophic benign 226650
  • Epidermolysis bullosa, junctional, Herlitz type 226700
  • Laryngoonychocutaneous syndrome 245660
Tags
monogenic-polygenic
OMIM
600805
Clinvar variants
Variants in LAMA3
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 LAMA3 was changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

19 Sep 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 Sep 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 Sep 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for LAMA3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

18 Sep 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for LAMA3 were set to Amelogenesis imperfecta, hypoplastic type; Epidermolysis bullosa, generalized atrophic benign 226650; Epidermolysis bullosa, junctional, Herlitz type 226700; Laryngoonychocutaneous syndrome 245660

16 Aug 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for LAMA3 were set to 22434185; 26502894; 27827380

12 Jun 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for LAMA3 were set to Amelogenesis Imperfecta

12 Jun 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for LAMA3 were set to 27827380

8 Jun 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for LAMA3 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)

LAMA3 was added to Amelogenesis Imperfectapanel. Source: UKGTN Model of inheritance for gene LAMA3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

8 Jun 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

LAMA3 was created by rfoulger

8 Jun 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

LAMA3 was added to Amelogenesis Imperfectapanel. Sources: Eligibility statement prior genetic testing