Amelogenesis imperfecta
Gene: LAMB3Comment when marking as ready: Marked as ready: October 31st 2017.Created: 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.Created: 31 Oct 2017, 2:29 p.m.
Comment when marking as ready: Marked as Ready: 18th October 2017.Created: 18 Oct 2017, 11:44 a.m.
Comment on mode of pathogenicity: Updated M.O.P to 'Other' in-line with Claire's comments.Created: 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.Created: 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'.Created: 16 Aug 2017, 9:42 a.m.
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/LAMB3Created: 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
This panel has been promoted after review by Claire Smith (Leeds) and further personal consultation with Dr Smith
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Mode of pathogenicity for LAMB3 was changed to Other - please provide details in the comments
This gene has been classified as Green List (High Evidence).
Mode of inheritance for LAMB3 was changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
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
Phenotypes for LAMB3 were set to Amelogenesis imperfecta, type IA, 104530; Amelogenesis Imperfecta, Type IA, 104530
Publications for LAMB3 were set to 24494736; 23632796; 23958762; 25769099; 7706760; 26502894; 27220909
LAMB3 was added to Amelogenesis Imperfectapanel. Source: UKGTN Model of inheritance for gene LAMB3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
LAMB3 was added to Amelogenesis Imperfectapanel. Source: Radboud University Medical Center, Nijmegen
LAMB3 was created by rfoulger
LAMB3 was added to Amelogenesis Imperfectapanel. Sources: Eligibility statement prior genetic testing