title: Identification of a de novo heterozygous missense FLNB mutation in lethal atelosteogenesis type I by exome sequencing.
abstract: BACKGROUND
  Atelosteogenesis type I (AO-I) is a rare lethal skeletal dysplastic disorder characterized by severe short-limbed dwarfism and dislocated hips, knees, and elbows. AO-I is caused by mutations in the filamin B (FLNB) gene; however, several other genes can cause AO-like lethal skeletal dysplasias.
  
  
  METHODS
  In order to screen all possible genes associated with AO-like lethal skeletal dysplasias simultaneously, we performed whole-exome sequencing in a female newborn having clinical features of AO-I.
  
  
  RESULTS
  Exome sequencing identified a novel missense variant (c.517G>A; p.Ala173Thr) in exon 2 of the FLNB gene in the patient. Sanger sequencing validated this variant, and genetic analysis of the patient's parents suggested a de novo occurrence of the variant.
  
  
  CONCLUSIONS
  This study shows that exome sequencing can be a useful tool for the identification of causative mutations in lethal skeletal dysplasia patients.
authors.affiliation: Department of Pediatrics, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea.
authors.forename: Ga Won
authors.initials: GW
authors.lastname: Jeon
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea.
authors.forename: Ji Mi
authors.initials: JM
authors.lastname: Jung
authors.affiliation: Department of Obstetrics and Gynecology, Catholic University of Daegu, Daegu Catholic University Medical Center, Daegu, Korea.
authors.forename: Seong Yeon
authors.initials: SY
authors.lastname: Hong
authors.affiliation: Department of Obstetrics and Gynecology, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea.
authors.forename: Young Nam
authors.initials: YN
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea.
authors.forename: Jong Beom
authors.initials: JB
authors.lastname: Sin
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
mesh_terms: D059472:Exome; D005260:Female; D064448:Filamins / Q000737:chemistry / Q000235:genetics*; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D020125:Mutation, Missense; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D017422:Sequence Analysis, DNA
chemical_list: D064448:Filamins
keywords: Atelosteogenesis type I; Exome sequencing; FLNB; Mutation