Analysis of FGFR3 Gene in Achondroplasia Patients: Application of Molecular Diagnosis

Abstract

Background: Achondroplasia is the most common form of dwarfism, characterized by disproportionate short stature and inherited in an autosomal dominant pattern. Its prevalence is approximately 1:10,000 to 1:30,000 live births. The substitution mutation, c.1138G>A, in the FGFR3 gene is responsible for 97 - 98% of achondroplasia cases. The similarity of other skeletal dysplasias caused by mutations in the FGFR3 gene complicates the diagnosis of achondroplasia. Therefore, the final diagnosis is confirmed through molecular testing and analysis of the FGFR3 gene. Objectives: This study aims to conduct a genetic examination of achondroplasia patients to identify the disease-causing mutation. Methods: A total of 10 achondroplasia patients participated in this study. All patients met the study's inclusion criteria, which included clinical symptoms and radiographic results consistent with achondroplasia, as determined by a pediatric endocrinologist. These patients were examined for the common mutation, c.1138G>A, in the FGFR3 gene using ARMS-PCR. Exons and adjacent intronic regions of FGFR3 in patients without the common mutation were also analyzed using Sanger sequencing. Results: The common mutation, c.1138G>A, was detected in eight patients by ARMS-PCR. In two other patients, the mutation, c.1620C>G, which is one of the most common mutations associated with hypochondroplasia, was identified. Validation of ARMS-PCR results with Sanger sequencing indicates 100% accuracy of this method. Conclusions: The final diagnosis of achondroplasia is crucial for managing complications and improving patients' quality of life, as well as providing genetic counseling for other family members. This diagnosis is achieved solely through genetic evaluation of achondroplasia patients. ARMS-PCR serves as a precise and reliable method for genetic evaluation and identifying patients with the common mutation.