Amelogenesis imperfecta

Gene: AMBN

The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 5 Dec 2024, 4:40 p.m. | Last Modified: 5 Dec 2024, 4:40 p.m.

Panel Version: 3.11

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Green List (high evidence)

Comment on mode of inheritance: There is sufficient evidence available for the association of both monoallelic and biallelic AMBN variants with amelogenesis imperfecta. However, only the autosomal recessive phenotype has been reported in OMIM.

The MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.

Created: 26 Jun 2024, 9 p.m. | Last Modified: 26 Jun 2024, 9 p.m.

Panel Version: 3.9

PMID:30174330 - One family was reported with monoallelic missense variant and amelogenesis imperfecta (AI) and dentin disorders.

PMID:31402633 - A family was reported with hypoplastic AI and biallelic (compound heterozygous) variants. In addition, Ambn knockout/NLS-lacZ (AmbnlacZ/lacZ ) knockin mice model supports gene-disease association.

PMID:38058155 - Five new pathogenic variants were reported in 11 unrelated families with AI, of which six families were identified with biallelic variants and five families were identified with monoallelic variants.

Created: 26 Jun 2024, 8:53 p.m. | Last Modified: 26 Jun 2024, 8:53 p.m.

Panel Version: 3.6

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Amelogenesis imperfecta, type IF, OMIM:616270

Publications

• 30174330
• 31402633
• 38058155

Comment when marking as ready: Marked as Ready: 4th September 2017.

Created: 4 Sep 2017, 12:13 p.m.

Added 'CNV' tag based on email correspondance from Claire Smith confirming a third case (a CNV).

Created: 4 Sep 2017, 12:13 p.m.

Comment on list classification: Updated rating from Amber to Green based on email correspondance with Claire Smith who confirmed a third case - a CNV (homozygous duplication of AMBN exons 7-11, exact breakpoints not yet defined).

Created: 4 Sep 2017, 12:12 p.m.

Comment on list classification: Updated rating from Red to Amber awaiting further clinical input: Green expert review and on Leeds diagnostic panel but only 2 cases reported to-date.

Created: 16 Aug 2017, 2:13 p.m.

Green List (high evidence)

PMID: 38058155 identifies AMBN variants that appear to cause disease in an autosomal dominant fashion.
One family has a dominant family history spanning 4 generations, and the likely causative variant in this family was also identified as monoallelic/heterozygous in 2 other apparently unrelated individuals with isolated AI.

Created: 2 May 2024, 2:08 p.m. | Last Modified: 2 May 2024, 2:08 p.m.

Panel Version: 3.3

Currently on the Leeds AI diagnostic panel (Contact: Ruth Charlton). Only two mutations have been reported in AMBN in AI patients, both discovered through Next Generation Sequencing (NGS). The first AMBN mutation reported, a large, in-frame deletion encompassing exon 6, segregated with recessive hypoplastic AI in a consanguineous Costa Rican family identified using whole exome sequencing. The second homozygous mutation, thought to alter splicing, was identified in one patient in a large cohort with oro-dental disease, using a targeted NGS assay. See AMBN LOVD: http://dna2.leeds.ac.uk/LOVD/genes/AMBN

Created: 3 Aug 2017, 1:47 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Amelogenesis imperfecta, type IF 616270

Publications

• PMID: 24858907
• 26502894
• 38058155