Amelogenesis imperfecta

Gene: LAMB3

Green List (high evidence)

LAMB3 (laminin subunit beta 3)
EnsemblGeneIds (GRCh38): ENSG00000196878
EnsemblGeneIds (GRCh37): ENSG00000196878
OMIM: 150310, Gene2Phenotype
LAMB3 is in 4 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Marked as ready: October 31st 2017.
31 Oct 2017, 2:31 p.m.
Comment on mode of inheritance: Updated MOI from just AD to 'both AD and AR' based on Claire Smith's comments that AI is part of Junctional Epidermolysis Bullosa, where biallelic LAMB3 variants are causative. Both AR and AD MOI also agreed with Arianna Tucci.
31 Oct 2017, 2:29 p.m.
Comment when marking as ready: Marked as Ready: 18th October 2017.
18 Oct 2017, 11:44 a.m.
Comment on mode of pathogenicity: Updated M.O.P to 'Other' in-line with Claire's comments.
18 Oct 2017, 11:44 a.m.
Comment on list classification: Updated rating from Amber to Green: Green expert review plus on Leeds diagnostic panel. 3 unrelated cases supporting causation of AI in OMIM (plus further JEB cases where AI may be a presenting phenotype), and further LAMB3 variants curated in LOVD.
16 Aug 2017, 1:35 p.m.
Comment on phenotypes: Added junctional Epidermolysis bullosa phenotypes based on comment by Claire Smith that AI phenotype is part of Junctional Epidermolysis Bullosa. Also, OMIM clinical synopsis for JEB disorders includes 'Enamel hypoplasia' and 'Dental caries'.
16 Aug 2017, 9:42 a.m.

Claire Smith (University of Leeds)

Green List (high evidence)

Currently on the Leeds AI diagnostic panel (Contact: Ruth Charlton). Only particular LAMB3 heterozygous variants cause AI. However AI is part of Junctional Epidermolysis Bullosa where biallelic LAMB3 variants are causative. The majority of AI-causing LAMB3 variants have not been reported in JEB patients. Most LAMB3 variants identified in AI patients are either frameshift or nonsense mutations predicted to escape NMD. The variants are consistent with a dominant gain of function disease mechanism, unlike the loss of function variants associated with recessively-inherited JEB. However, Prasad et al. (2016) did identify two AI patients carrying LAMB3 mutations that do not fit this pattern of pathogenesis, although family members for segregation purposes were lacking in these two cases and proof of causation was not ascertained. See LAMB3 LOVD: http://dna2.leeds.ac.uk/LOVD/genes/LAMB3
3 Aug 2017, 1:34 p.m.

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

Phenotypes
Amelogenesis imperfecta, type IA 104530; Epidermolysis bullosa, junctional, Herlitz type 226700; Epidermolysis bullosa, junctional, non-Herlitz type 226650

Publications

Mode of pathogenicity
Other

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
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Amelogenesis imperfecta, type IA, 104530
  • Amelogenesis Imperfecta, Type IA, 104530
  • Epidermolysis bullosa, junctional, Herlitz type, 26700
  • Epidermolysis bullosa, junctional, non-Herlitz type, 226650
OMIM
150310
Clinvar variants
Variants in LAMB3
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

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).

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).

18 Oct 2017, Gel status: 4

Set mode of pathogenicity

Rebecca Foulger (Genomics England curator)

Mode of pathogenicity for LAMB3 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 LAMB3 was changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

16 Aug 2017, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for LAMB3 were set to Amelogenesis imperfecta, type IA, 104530; Amelogenesis Imperfecta, Type IA, 104530; Epidermolysis bullosa, junctional, Herlitz type, 26700; Epidermolysis bullosa, junctional, non-Herlitz type, 226650

16 Aug 2017, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for LAMB3 were set to Amelogenesis imperfecta, type IA, 104530; Amelogenesis Imperfecta, Type IA, 104530

16 Aug 2017, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for LAMB3 were set to 24494736; 23632796; 23958762; 25769099; 7706760; 26502894; 27220909

8 Jun 2017, Gel status: 2

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

LAMB3 was added to Amelogenesis Imperfectapanel. Source: UKGTN Model of inheritance for gene LAMB3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

8 Jun 2017, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

LAMB3 was added to Amelogenesis Imperfectapanel. Source: Radboud University Medical Center, Nijmegen

8 Jun 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

LAMB3 was created by rfoulger

8 Jun 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

LAMB3 was added to Amelogenesis Imperfectapanel. Sources: Eligibility statement prior genetic testing