title: Novel Deletion of SERPINF1 Causes Autosomal Recessive Osteogenesis Imperfecta Type VI in Two Brazilian Families.
abstract: Autosomal recessive osteogenesis imperfecta (OI) accounts for 10% of all OI cases, and, currently, mutations in 10 genes (CRTAP, LEPRE1, PPIB, SERPINH1, FKBP10, SERPINF1, SP7, BMP1, TMEM38B, and WNT1) are known to be responsible for this form of the disease. PEDF is a secreted glycoprotein of the serpin superfamily that maintains bone homeostasis and regulates osteoid mineralization, and it is encoded by SERPINF1, currently associated with OI type VI (MIM 172860). Here, we report a consanguineous Brazilian family in which multiple individuals from at least 4 generations are affected with a severe form of OI, and we also report an unrelated individual from the same small city in Brazil with a similar but more severe phenotype. In both families the same homozygous SERPINF1 19-bp deletion was identified which is not known in the literature yet. We described intra- and interfamilial clinical and radiological phenotypic variability of OI type VI caused by the same homozygous SERPINF1 19-bp deletion and suggest a founder effect. Furthermore, the SERPINF1 genotypes/phenotypes reported so far in the literature are reviewed.
authors.affiliation: Center of Medical Genetics, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Renata Moldenhauer
authors.initials: RM
authors.lastname: Minillo
authors.affiliation: McKusick-Nathan Institute of Genetic Medicine, Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Md., USA.
authors.forename: Nara
authors.initials: N
authors.lastname: Sobreira
authors.affiliation: Center of Medical Genetics, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Maria de Fatima
authors.initials: Mde F
authors.lastname: de Faria Soares
authors.affiliation: McKusick-Nathan Institute of Genetic Medicine, Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Md., USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Jurgens
authors.affiliation: Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Md., USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Ling
authors.affiliation: Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Md., USA.
authors.forename: Kurt N
authors.initials: KN
authors.lastname: Hetrick
authors.affiliation: Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Md., USA.
authors.forename: Kimberly F
authors.initials: KF
authors.lastname: Doheny
authors.affiliation: McKusick-Nathan Institute of Genetic Medicine, Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Md., USA.
authors.forename: David
authors.initials: D
authors.lastname: Valle
authors.affiliation: Center of Medical Genetics, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Decio
authors.initials: D
authors.lastname: Brunoni
authors.affiliation: Center of Medical Genetics, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Ana B Alvarez
authors.initials: AB
authors.lastname: Perez
keywords: Autosomal recessive; Osteogenesis imperfecta type VI; SERPINF1