Normal bone density and fat mass in heterozygous SERPINF1 mutation carriers

Area of Science:

• Genetics and Molecular Biology
• Endocrinology and Metabolism
• Orthopedics

Background:

• Homozygous SERPINF1 mutations cause osteogenesis imperfecta type VI due to pigment epithelium-derived factor (PEDF) deficiency.
• The phenotypic consequences of heterozygous SERPINF1 mutations remain unknown.

Purpose of the Study:

• To investigate whether heterozygous SERPINF1 mutations are associated with a clinical phenotype.
• To compare health outcomes between carriers and non-carriers of SERPINF1 mutations within families affected by osteogenesis imperfecta type VI.

Main Methods:

• Assessed 29 family members of patients with osteogenesis imperfecta type VI, including 18 heterozygous SERPINF1 mutation carriers.
• Measured PEDF expression in skin fibroblasts, skeletal characteristics (bone density via DXA and pQCT), body composition, and serum markers of bone metabolism, lipids, and PEDF.
• Compared carriers and non-carriers of SERPINF1 mutations.

Main Results:

• Heterozygous SERPINF1 mutation carriers exhibited reduced SERPINF1 transcript levels and significantly lower mean PEDF serum concentrations compared to non-carriers (P = .04).
• No significant differences were observed between carriers and non-carriers in bone density (lumbar spine, total body, radius, tibia), body composition, lipid status, or bone metabolism markers.

Conclusions:

• Despite decreased pigment epithelium-derived factor (PEDF) expression, individuals with heterozygous SERPINF1 mutations do not present with detectable abnormalities in bone or fat.
• These findings suggest that heterozygous SERPINF1 mutations may not lead to a clinically apparent phenotype related to bone or metabolic health.