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Updated: Feb 2, 2026

Electroporation of Craniofacial Mesenchyme
Published on: November 28, 2011
Six NSCL/P Loci Show Associations With Normal-Range Craniofacial Variation
Karlijne Indencleef1,2, Jasmien Roosenboom3, Hanne Hoskens2,4
1Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium.
Genetic variants linked to non-syndromic cleft lip with/without cleft palate (NSCL/P) also influence normal facial shape. This study found specific genetic variations associated with NSCL/P affect features like the chin, nose, and philtrum in the general population.
Area of Science:
- Genetics
- Craniofacial Biology
- Human Morphology
Background:
- Orofacial clefting is a common craniofacial malformation.
- Unaffected relatives of NSCL/P patients exhibit distinct facial features, suggesting shared genetic influences.
- Genes implicated in clefting may also play a role in normal craniofacial development.
Purpose of the Study:
- To investigate the impact of genetic variants associated with non-syndromic cleft lip with/without cleft palate (NSCL/P) on normal facial shape variation.
- To explore the hypothesis that NSCL/P susceptibility genes influence typical craniofacial development.
Main Methods:
- Literature review of GWAS for NSCL/P identified 75 single nucleotide polymorphisms (SNPs) in 38 loci.
- Genotype and 3D facial image data from 7,418 European ancestry participants were analyzed.
- Multivariate canonical correlation analysis (CCA) and meta-analysis assessed SNP effects on 63 facial segments.
Main Results:
- Six NSCL/P-associated SNPs significantly correlated with normal-range facial morphology variations.
- Specific SNPs impacted the chin (rs6740960), philtrum (rs227731 near NOG), nose (rs742071, rs34246903, rs10512248), and supraorbital ridge (rs7590268).
- Significant associations were found for genes including NOG, PAX7, MSX1, PTCH1, and THADA.
Conclusions:
- Genetic variants associated with NSCL/P contribute to normal variation in craniofacial morphology.
- Significant effects were observed in the chin, nose, supraorbital ridges, and philtrum.
- This provides evidence for a shared genetic basis between clefting disorders and typical facial development.
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