Identification of a Novel FGFR2 Gene Mutation (c.514_515delinsCT, p.Ala172Leu) in a Chinese Neonate With Apert...

Apert syndrome (AS) is a rare autosomal dominant congenital disorder characterized by craniosynostosis, midfacial hypoplasia, and syndactyly. Most cases are caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene, primarily S252W and P253R mutations, more than 98% resulting from de novo mutations. The FGFR2 gene encodes a receptor tyrosine kinase protein, which is essential for embryonic development and skeletal formation. The study reported a Chinese newborn diagnosed with AS, attributed to a novel FGFR2 gene mutation, c.514_515delinsCT (p. Ala172Leu), identified through whole exome sequencing (WES). The proband was a male infant born at 38⁺⁵ weeks of gestation to non-consanguineous parents. At birth, he exhibited craniofacial abnormalities, including frontal bossing, proptosis, hypertelorism, and a hooked nose, along with syndactyly of the hands and feet. Additional findings included congenital heart defects, bronchial stenosis, and hyperhidrosis. Genetic testing revealed a novel FGFR2 mutation, c.514_515delinsCT (p. Ala172Leu), which was absent in his parents, confirming a de novo mutation. Protein structure prediction using AlphaFold and PyMOL demonstrated significant structural differences between the wild-type and mutant proteins, with an RMSD value of 11.147 Å. This mutation likely disrupts FGFR2's ligand-binding ability, leading to aberrant activation and contributing to the clinical features observed. This case presents a novel FGFR2 mutation, expanding the spectrum of genetic variants associated with AS. The findings underscore the importance of genetic testing and protein structure analysis in diagnosing atypical cases and understanding genotype-phenotype correlations. Further studies with larger cohorts are needed to elucidate the molecular mechanisms underlying AS and develop personalized diagnostic and therapeutic approaches for this complex disorder.