Amelogenesis imperfectaGene: ITGB4
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, 2:37 p.m.
Comment on mode of inheritance: Monoallelic MOI taken from UKGTN gene dosier for 21-gene Amelogenesis imperfecta panel. JEB phenotypes (MIM:226730 and MIM:226650) have biallelic (AR) inheritance but UKGTN predicts a monoallelic inheritance based on the presence of AI in JEB carriers for COLA17A1, LAMA3 and LAMB3.
Created: 19 Oct 2017, 1:25 p.m.
Comment on list classification: Updated rating from Red to Amber, awaiting expert review. Although ITGB4 appears in the 'prior genetic testing' inclusion list and on the UKGTN 21-gene AI panel, the evidence is indirect and not yet verified, being based largely on AI symptoms in JEB carriers heterozygous for variants in other (non-ITGB4) genes.
Created: 19 Oct 2017, 1:06 p.m.
PMID:12485428 report a 49 year old female with mild blistering of hands and feet and enamel hypoplasia. The phenotype was caused by a novel 2bp heterozygous deletion (4733delCT) in ITGB4, resulting in in-frame skipping of exon 36 and a deduced 50 amino acid deletion. The authors expect that this heterozygous variant is accompanied by an additional heterozygous null allele.
Created: 19 Oct 2017, 12:59 p.m.
UKGTN dosier for 21-gene AI panel states: Good candidate as ITGB4 mutations cause JEB with pyloric atresia, which includes enamel defects as a feature. Isolated AI has been observed in heterozygous relatives of JEB patients with variants in COL17A1, LAMA3 and LAMB3. Therefore it is possible that heterozygous ITGB4 variants could cause AI in isolation also.
Created: 19 Oct 2017, 12:50 p.m.
This panel has been promoted after review by Claire Smith (Leeds) and further personal consultation with Dr Smith
Mode of inheritance for ITGB4 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for ITGB4 were set to Amelogenesis Imperfecta; Epidermolysis bullosa, junctional, with pyloric atresia, 226730 (includes Enamel hypoplasia); Epidermolysis bullosa, junctional, non-Herlitz type, 226650 (includes enamel pitting)
This gene has been classified as Amber List (Moderate Evidence).
Mode of inheritance for ITGB4 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
ITGB4 was added to Amelogenesis Imperfectapanel. Source: UKGTN Model of inheritance for gene ITGB4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
ITGB4 was added to Amelogenesis Imperfectapanel. Sources: Eligibility statement prior genetic testing
ITGB4 was created by rfoulger