Apert syndrome with S252W FGFR2 mutation and characterization using Phenomizer: An Indian case report

Area of Science:

• Medical Genetics
• Clinical Diagnostics
• Bioinformatics

Background:

• Accurate diagnosis of human genetic diseases is crucial for effective clinical management, prenatal detection, and genetic counseling.
• Interpreting genotypic and phenotypic heterogeneity requires advanced phenotyping alongside DNA sequencing.
• Craniosynostosis syndromes, characterized by premature skull fusion, necessitate precise differential diagnosis.

Purpose of the Study:

• To demonstrate the utility of human ontology-based phenotypic characterization using Phenomizer for genetic disease diagnosis.
• To investigate a case of craniosynostosis and identify the underlying genetic mutation.
• To showcase the integration of phenotypic analysis with molecular genetics for improved diagnostic accuracy.

Main Methods:

• Utilized Phenomizer, a web-based tool employing human ontology for phenotypic characterization.
• Inputted specific phenotypic features of a craniosynostosis patient into Phenomizer.
• Performed molecular genetic analysis to confirm gene mutations suggested by Phenomizer.

Main Results:

• Phenomizer analysis indicated a high probability of mutation in the FGFR2 gene based on the patient's phenotype.
• Genetic analysis identified a specific mutation (c.755C>G) in the FGFR2 gene.
• The identified mutation confirmed a diagnosis of Apert syndrome, a severe craniosynostosis syndrome.

Conclusions:

• Phenomizer is a valuable tool for statistical scoring of potential diagnoses in genetic diseases.
• Integrating Phenomizer with molecular genetic analysis enhances the differential diagnosis of complex genetic conditions.
• This case underscores the importance of advanced phenotyping tools in identifying specific genetic mutations and syndromes like Apert syndrome.