Normal bone density and fat mass in heterozygous SERPINF1 mutation carriers.

CONTEXT Homozygous mutations in SERPINF1 cause deficiency of pigment epithelium-derived factor (PEDF) and lead to osteogenesis imperfecta (OI) type VI, but it is not known whether heterozygous mutations in SERPINF1 cause a phenotype. OBJECTIVE In the present study, we therefore assessed family members of individuals with OI type VI and compared the results of SERPINF1 mutation carriers with those of noncarriers of SERPINF1 mutations. SETTING This study was conducted at a metabolic bone clinic of a pediatric orthopedic hospital. SUBJECTS The study population comprised 29 family members (age range 8-89 y; 18 females, 11 males) of patients with a diagnosis of OI type VI. Eighteen individuals were heterozygous for SERPINF1 mutations, but the others did not carry a mutation. MAIN OUTCOME MEASURES PEDF expression was assessed in skin fibroblasts from four heterozygous SERPINF1 mutation carriers. Skeletal characteristics and body composition were measured using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Serum samples were used to quantify markers of bone metabolism, lipid status, and PEDF. RESULTS Carriers of heterozygous stop or frame shift mutations in SERPINF1 had low SERPINF1 transcript levels. Mean PEDF serum concentrations were significantly lower in the carrier group than in the noncarriers (P = .04). However, no group differences were found with regard to areal bone density at the lumbar spine and total body, volumetric bone density at the radius and tibia, body composition, lipid status, and markers of bone metabolism. CONCLUSION Heterozygous SERPINF1 mutation carriers had no detectable abnormalities in fat and bone, despite decreased PEDF expression.