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Amelogenesis imperfecta v4.5 LAMC2 Eleanor Williams Classified gene: LAMC2 as Amber List (moderate evidence)
Amelogenesis imperfecta v4.5 LAMC2 Eleanor Williams Added comment: Comment on list classification: Keeping the rating as amber. 1 reported case (PMID: 37228816) but with no phenotype for the mother who also carries the variant in LAMC2. Supportive mouse model in (PMID:26956061).
Amelogenesis imperfecta v4.5 LAMC2 Eleanor Williams Gene: lamc2 has been classified as Amber List (Moderate Evidence).
Amelogenesis imperfecta v4.4 LAMC2 Eleanor Williams Phenotypes for gene: LAMC2 were changed from Amelogenesis Imperfecta; Epidermolysis bullosa, junctional, Herlitz type, 226700; Epidermolysis bullosa, junctional, non-Herlitz type, 226650 to amelogenesis imperfecta, MONDO:0019507
Amelogenesis imperfecta v4.3 LAMC2 Eleanor Williams Added comment: Comment on mode of inheritance: Updating the mode of inheritance to monoallelic since in the only reported case the proband was heterozygous for a variant in LAMC2.
Amelogenesis imperfecta v4.3 LAMC2 Eleanor Williams Mode of inheritance for gene: LAMC2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Amelogenesis imperfecta v4.2 LAMC2 Eleanor Williams Publications for gene: LAMC2 were set to 26956061
Amelogenesis imperfecta v4.1 LAMC2 Claire Smith edited their review of gene: LAMC2: Added comment: PMID: 37228816 Bloch-Zupan et al. 2023 report one family with LAMC2 mutations as part of a larger panel of sequenced individuals. They report a single child as being affected with a hypoplastic/hypomature AI phenotype. The primary dentition is described as showing thin white opaque enamel.

They identified a heterozygous LAMC2 variant NM_005562.3: c.493C>T; p.(Arg165Cys) with an allele frequency of 0.2% in GnomAD, predicted deleterious by SIFT (v4.0.3) and PolyPhen-2 and located in the Laminin EGF domain. The authors highlight that the enamel formation defects in mice (Wazen et al., 2016) and the patient’s phenotype are similar to the one another. The allele is inherited from her mother but the mother's phenotype was not available.

Notably the patient was sequenced using whole exome sequencing using the following parameters: Non-pathogenic variants were filtered out via: 1) variants represented with an allele frequency of more than 1% in public variation databases including the 1,000 Genomes, the GnomAD database or their internal exome database, variants in 5′ or 3′ UTR, variants with intronic locations and no prediction of local splice effect, and synonymous variants without pathogenic prediction of local splice effect.

Annotations of structural variations (SV) were performed by AnnotSV (Geoffroy et al., 2018). No other findings are presented for the individual.

In conclusion, I do not believe this is strong enough evidence to conclude that this LAMC2 mutation is the cause of disease in this family due to the lack of phenotype information for the mother or any modelling of the effects of the variant, but it is suggestive and additional publications with further families might provide more solid evidence to elevate this gene to green. I would currently consider this gene to be rated amber.; Changed rating: AMBER; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Amelogenesis imperfecta LAMC2 Rebecca Foulger classified LAMC2 as amber
Amelogenesis imperfecta LAMC2 Rebecca Foulger marked LAMC2 as ready
Amelogenesis imperfecta LAMC2 Rebecca Foulger classified LAMC2 as red
Amelogenesis imperfecta LAMC2 Claire Smith reviewed LAMC2
Amelogenesis imperfecta LAMC2 Rebecca Foulger edited their review of LAMC2
Amelogenesis imperfecta LAMC2 Rebecca Foulger commented on LAMC2