Novel Mutations in SERPINF1 Result in Rare Osteogenesis Imperfecta Type VI

Area of Science:

• Genetics and Molecular Biology
• Orthopedics and Bone Diseases
• Rare Genetic Disorders

Background:

• Osteogenesis Imperfecta (OI) encompasses inherited disorders causing recurrent bone fractures.
• Mutations in the Serpin peptidase inhibitor, clade F, member 1 (SERPINF1) gene are associated with an extremely rare autosomal recessive form of OI type VI.
• Previous research has not identified SERPINF1 mutations in Chinese OI patient populations.

Purpose of the Study:

• To identify SERPINF1 gene mutations in Chinese patients diagnosed with Osteogenesis Imperfecta.
• To characterize the clinical and molecular phenotypes of OI patients with SERPINF1 mutations.
• To evaluate the diagnostic utility of serum pigment epithelium-derived factor (PEDF) levels in Chinese OI type VI patients.

Main Methods:

• A targeted next-generation sequencing panel for OI-related genes was developed.
• Pathogenic mutations were confirmed using Sanger sequencing and co-segregation analysis.
• Phenotypic evaluation included bone mineral density, radiological fracture assessment, bone turnover markers, and serum PEDF concentration.

Main Results:

• Six pathogenic SERPINF1 mutations were identified in six patients from five unrelated Chinese families, with five mutations being novel.
• Patients presented with moderate-to-severe bone fragility, low bone mineral density, and significant limb deformities.
• Serum PEDF levels were found to be barely detectable in nearly all affected individuals.

Conclusions:

• This study reports the first detection of SERPINF1 mutations in Chinese patients with Osteogenesis Imperfecta type VI.
• The identification of five novel SERPINF1 mutations expands the known mutational spectrum for this rare OI subtype.
• Serum PEDF levels are confirmed as a valuable diagnostic marker for OI type VI in the Chinese population.