Genetic Analysis Using a Next Generation Sequencing-Based Gene Panel in Patients With Skeletal Dysplasia: A...

Area of Science:

• Genetics
• Medical Diagnostics
• Rare Diseases

Background:

• Skeletal dysplasia (SD) encompasses a diverse group of rare genetic disorders with varied clinical presentations.
• Accurate clinical and genetic diagnosis of SD is challenging for healthcare professionals.
• Next-generation sequencing (NGS) has emerged as a powerful tool for genetic diagnosis of SD.

Purpose of the Study:

• To evaluate the diagnostic yield of targeted NGS gene panel sequencing in patients with suspected skeletal dysplasia.
• To identify causative genetic variants in a cohort of patients with suspected SD.

Main Methods:

• Targeted NGS of 437 genes associated with SD (based on 2019 nosology) was performed on 31 patients.
• Clinical and genetic data were analyzed to confirm diagnoses and identify pathogenic variants.

Main Results:

• A diagnostic yield of 51.9% was achieved, with 16 out of 31 patients receiving confirmed diagnoses.
• Eighteen pathogenic variants were identified in 13 genes, including four novel variants.
• Higher diagnostic rates were observed in patients with suspected familial SD and clear radiological evidence (73.3%).

Conclusions:

• NGS-based gene panel sequencing is effective for diagnosing genetically heterogeneous skeletal dysplasias.
• Patient categorization based on clinical features, family history, and radiographic findings can improve diagnostic yield.