| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ectodermal dysplasia v3.7 | LRP6 | Mafalda Gomes Publications for gene: LRP6 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.6 | LRP6 | Mafalda Gomes Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.6 | LRP6 |
Mafalda Gomes edited their review of gene: LRP6: Added comment: Massink et al. (2015) report the first association between LRP6 and oligodontia. LRP6 is a major component of the Wnt receptor complex in the canonical Wnt pathway. Other genes involved in this pathway, such as WNT10A, have been shown to be associated with oligodontia as well. 4 unrelated individuals with nonsyndromic oligodontia (12-20 missing teeth each) are reported: 3 carry heterozygous truncating variants in the LRP6 gene, and 1 carries a missense variant (p.Ala19Val) of a conserved residue located at the cleavage site of the protein's signal peptide. Functional studies showed that the missense variant results in altered glycosylation and improper subcellular localisation of the protein, resulting in abrogated activation of the Wnt pathway. Segregation studies confirmed presence of the variants in 6 additional affected family members across the 3 families with truncating variants. Incomplete penetrance was observed in the family of the individual with the missense variant, where the mother was found to be a carrier and is unaffected. Lastly, an affected father and 2 daughters showed minor anatomical variation of the ear and underdevelopment of the thumb. No other anomalies described in the cohort. Ockeloen et al. (2016) report 2 additional probands with oligodontia, one of which also had orofacial cleft, and perform a study among 67 patients with tooth agenesis, 1,073 patients with orofacial clefts, and 706 controls. They found significant enrichment of LRP6 rare variants in patients with tooth agenesis, but not in patients with nonsyndromic orofacial clefts. Five variants were identified in patients with tooth agenesis and shown to segregate in the 4 families (1 variant was de novo). Immunochemistry studies on embryonic mice showed that the gene is expressed in areas of bone formation, including the tooth follicle, suggesting a role in early tooth development. Therefore, this gene should be promoted GREEN in this panel.; Changed rating: GREEN; Changed phenotypes to: Tooth agenesis, selective, 7, OMIM:616724 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.6 | LRP6 | Mafalda Gomes Phenotypes for gene: LRP6 were changed from to Tooth agenesis, selective, 7, OMIM:616724 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.5 | LRP6 | Mafalda Gomes Classified gene: LRP6 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.5 | LRP6 | Mafalda Gomes Gene: lrp6 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.4 | LRP6 | Mafalda Gomes Tag Q3_23_promote_green tag was added to gene: LRP6. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.4 | LRP6 | Mafalda Gomes reviewed gene: LRP6: Rating: AMBER; Mode of pathogenicity: None; Publications: 26387593, 26963285; Phenotypes: Tooth agenesis, selective, 7; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ectodermal dysplasia v3.4 | LRP6 |
Mafalda Gomes gene: LRP6 was added gene: LRP6 was added to Ectodermal dysplasia. Sources: Literature Mode of inheritance for gene: LRP6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Penetrance for gene: LRP6 were set to Incomplete |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||