title: Normal bone density and fat mass in heterozygous SERPINF1 mutation carriers.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This study was conducted at a metabolic bone clinic of a pediatric orthopedic hospital.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Heterozygous SERPINF1 mutation carriers had no detectable abnormalities in fat and bone, despite decreased PEDF expression.
authors.affiliation: Shriners Hospital for Children and McGill University, Montréal, Québec, Canada H3G 1A6.
authors.forename: Hadil
authors.initials: H
authors.lastname: Al-Jallad
authors.forename: Telma
authors.initials: T
authors.lastname: Palomo
authors.forename: Pierre
authors.initials: P
authors.lastname: Moffatt
authors.forename: Peter
authors.initials: P
authors.lastname: Roughley
authors.forename: Francis H
authors.initials: FH
authors.lastname: Glorieux
authors.forename: Frank
authors.initials: F
authors.lastname: Rauch
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D055815:Young Adult; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor