title: PCSK5 mutation in a patient with the VACTERL association.
abstract: BACKGROUND
  The VACTERL association is a typically sporadic, non-random collection of congenital anomalies that includes vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, renal anomalies, and limb abnormalities. Although several chromosomal aberrations and gene mutations have been reported as disease-causative, these findings have been sparsely replicated to date.
  
  
  METHODS
  In the present study, whole exome sequencing of a case with the VACTERL association uncovered a novel frameshift mutation in the PCSK5 gene, which has been reported as one of the causative genes for the VACTERL association. Although this mutation appears potentially pathogenic in its functional aspects, it was also carried by the healthy father. Furthermore, a database survey revealed several other deleterious variants in the PCSK5 gene in the general population.
  
  
  CONCLUSIONS
  Further studies are necessary to clarify the etiological role of the PCSK5 mutation in the VACTERL association.
authors.affiliation: Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan. yxn14@aol.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: DNA Chip Research Inc., Kanagawa, Japan. s-kikugawa@dna-chip.co.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kikugawa
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama, Japan. seki@med.u-toyama.ac.jp.
authors.forename: Shoji
authors.initials: S
authors.lastname: Seki
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan. takamasa@med.hokudai.ac.jp.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahata
authors.affiliation: Department of Orthopaedic Surgery, Hokkaido University School of Medicine, Sapporo, Japan. niwasaki38@yahoo.co.jp.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Iwasaki
authors.affiliation: Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. hterai@med.osaka-cu.ac.jp.
authors.forename: Hidetomi
authors.initials: H
authors.lastname: Terai
authors.affiliation: Department of Orthopaedic Surgery, Nagano Prefectural Children's Hospital, Azumino, Japan. matsubara7942@yahoo.co.jp.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Matsubara
authors.affiliation: Department of Orthopaedic Surgery, Nagano Prefectural Children's Hospital, Azumino, Japan. fujioka-fumio-r@pref-nagano-hosp.jp.
authors.forename: Fumio
authors.initials: F
authors.lastname: Fujioka
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan. hinagaki@fujita-hu.ac.jp.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Inagaki
authors.affiliation: Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. tkobayashi1@partners.org.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama, Japan. tkimura@med.u-toyama.ac.jp.
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan. kura@fujita-hu.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
authors.affiliation: Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan. hirokato@shinshu-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
mesh_terms: D001003:Anal Canal / Q000002:abnormalities* / Q000201:enzymology; D002648:Child; D004252:DNA Mutational Analysis; D004947:Esophagus / Q000002:abnormalities* / Q000201:enzymology; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D040941:Heredity; D006801:Humans; D007668:Kidney / Q000002:abnormalities* / Q000201:enzymology; D017880:Limb Deformities, Congenital / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010641:Phenotype; D045702:Proprotein Convertase 5 / Q000235:genetics*; D013131:Spine / Q000002:abnormalities* / Q000201:enzymology; D014132:Trachea / Q000002:abnormalities* / Q000201:enzymology
chemical_list: C000599273:PCSK5 protein, human; D045702:Proprotein Convertase 5