Related Experiment Video
Updated: Jan 13, 2026
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
LRP6 β-Propeller Destabilization: Novel Variant, Phenotype and Diagnostic Implications in Tooth Agenesis
Narin Intarak1, Tohid Ghasemnejad2, Kausar Sadia Fakhruddin3
1Center of Excellence in Precision Medicine and Digital Health, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Background And Objectives:
Oligodontia, the congenital absence of multiple permanent teeth, is frequently linked to LRP6 variants. However, the genotype-phenotype correlations remain unclear and non-European cohorts are underrepresented. The objectives of this study were to: (1) characterize the molecular and clinical features of LRP6 variants identified in unrelated Thai individuals with tooth agenesis; (2) conduct a scoping review of previously published cases; and (3) refine the understanding of LRP6 genotype-phenotype correlations.
Materials And Methods:
A detailed case series analysis of Thai families with congenital tooth agenesis (through exome sequencing and 3D protein modelling) was conducted, and functional validation was performed using computational structural prediction. A reviewed published cases of LRP6 variants was performed following a PRISMA-ScR-guided scoping review (2005-2025).
Results:
p.Asp411Tyr, a novel heterozygous de novo missense change, destabilised the β-propeller domain. While Thai probands expanded the phenotype and genotype spectrum of LRP6-associated tooth agenesis, a review of 20 studies showed clustering of variants in β-propeller domains (62%), usually autosomal dominant (78%) but with variable penetrance. The phenotypes ranged from isolated oligodontia to syndromic forms. Thai probands displayed rare ectodermal-associated features (preauricular pits, dry skin) expanding the spectrum.
Conclusions:
LRP6 is a mutational hotspot in tooth development, with variable phenotypical expressivity and penetrance.
