Global First: Xinjiang Medical University Discovers Potential Association Between PAX7 Gene Variant and Rare Craniofacial Duplication Malformation

*Source: "Duplicated and Displaced Upper Lip and Maxilla: An Extremely Rare Congenital Craniofacial Malformation with Novel Genetic Findings"

DentalGoodNews｜Recently, a research team from the First Affiliated Hospital of Xinjiang Medical University published a study in the international journal Journal of Oral Pathology & Medicine, reporting for the first time globally a potential association between PAX7 gene variants and craniofacial duplication malformation (Diprosopus).

Craniofacial duplication malformation is a rare subtype of conjoined twins involving partial or complete duplication of craniofacial structures. According to data in the paper, since the first report in 1948, fewer than 40 cases have been documented in global literature, and the pathogenesis has long lacked clear explanation. According to official disclosure, based on the successful treatment of an extremely rare "craniofacial duplication malformation" (Diprosopus) patient, the research team discovered for the first time that specific PAX7 gene mutations may be associated with this disease.

*Source: "Duplicated and Displaced Upper Lip and Maxilla: An Extremely Rare Congenital Craniofacial Malformation with Novel Genetic Findings"

Building on the treatment foundation, the research team further conducted whole-exome sequencing (WES) analysis on samples from the patient and their mother, detecting a PAX7 gene missense mutation (c.1033G>C, p.Ala345Pro) in both. This mutation is located in the functional region of the PAX7 protein. Bioinformatics analysis shows that this site has high conservation across different species, and multiple prediction tools suggest that this variant may impact protein structure and function. However, since the patient's father was deceased, the study could not obtain paternal genetic samples, making it impossible to determine whether this variant was maternally inherited or a de novo mutation in the maternal generation.

Researchers point out that the PAX7 gene encodes a paired box transcription factor that plays an important role during embryonic development. Previous studies have shown that PAX7 has critical regulatory functions in the formation, differentiation, and migration of neural crest cells. During weeks 4-8 of human embryonic development, a critical period for craniofacial structure formation, PAX7-expressing cranial neural crest cells migrate from the dorsal neural tube to the first branchial arch and further differentiate to form important structures such as the maxilla and mandible.

Therefore, the research team speculates that if PAX7 function is disrupted during this critical stage, it may participate in the occurrence of craniofacial structural abnormalities by affecting neural crest cell migration or fate determination.

*Source: "Duplicated and Displaced Upper Lip and Maxilla: An Extremely Rare Congenital Craniofacial Malformation with Novel Genetic Findings"

It is worth noting that researchers point out that this finding currently only suggests a potential association and does not prove causality. The variant also exists in the phenotypically normal mother, suggesting possible incomplete penetrance, variable expressivity, or the need for other genetic and environmental factors to act together.

Future work still requires in vitro functional experiments (such as luciferase reporter gene assays, DNA binding experiments) and animal model studies (such as zebrafish or mouse models) to verify the pathogenicity of this variant. Meanwhile, the research team calls for establishing an international case registry system and expanding genetic screening scope to help clarify the relationship between genotype and phenotype.

*Source: Xinjiang Medical University

According to official disclosure, this research achievement was presented at the National Academic Conference of the Chinese Stomatological Association and was selected as one of the top 100 excellent cases in the 2025 China Clinical Case Achievement Database by the China Association for Science and Technology.