title: Hereditary interstitial lung diseases manifesting in early childhood in Japan.
abstract: BACKGROUND
  Genetic variations associated with interstitial lung diseases (ILD) have not been extensively studied in Japanese infants.
  
  
  METHODS
  Forty-three infants with unexplained lung dysfunction were studied. All 43, 22, and 17 infants underwent analyses of surfactant protein (SP)-C gene (SFTPC) and ATP-binding cassette A3 gene (ABCA3), SP-B gene (SFTPB), and SP-B western blotting, respectively. Two and four underwent assessment of granulocyte macrophage colony-stimulating factor-stimulating phosphorylation of signal transducer and activator of transcription-5 (pSTAT-5) and analyses of FOXF1 gene (FOXF1), respectively.
  
  
  RESULTS
  ILD were diagnosed clinically in nine infants: four, three, and two had interstitial pneumonitis, hereditary pulmonary alveolar proteinosis (hPAP), and alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), respectively. Genetic variations considered responsible were detected in six (67%) of the nine infants with ILD: three with hPAP (SFTPC p.Leu45Arg and p.Gln145fs, and ABCA3 p.Arg1583Trp/p.Val1495CysfsX21), two with interstitial pneumonitis (SFTPC p.Lys63Glu and p.Ser72Asn/p.Gly100Ala), and one with ACD/MPV (FOXF1 p.Leu300ArgfsX79). None showed SFTPB mutations or defects in pSTAT-5. The 17 bronchoalveolar lavage or tracheal aspirates contained enough SP-B protein.
  
  
  CONCLUSIONS
  The SP-C abnormality was most prevalent, and SP-B deficiency was rare in Japanese infants with hereditary ILD.
authors.affiliation: Maternity and Perinatal Care Center, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Akimoto
authors.affiliation: Maternity and Perinatal Care Center, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Cho
authors.affiliation: Maternity and Perinatal Care Center, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Hayasaka
authors.affiliation: Maternity and Perinatal Care Center, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Morioka
authors.affiliation: Maternity and Perinatal Care Center, Hokkaido University Hospital, Sapporo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kaneshi
authors.affiliation: Department of Obstetrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Itsuko
authors.initials: I
authors.lastname: Furuta
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
authors.affiliation: Department of Obstetrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Minakami
mesh_terms: D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D040941:Heredity; D007564:Japan / Q000453:epidemiology; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D017563:Lung Diseases, Interstitial / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D010641:Phenotype; D010766:Phosphorylation; D011649:Pulmonary Alveolar Proteinosis / Q000151:congenital / Q000208:ethnology / Q000235:genetics; D037701:Pulmonary Surfactant-Associated Protein B / Q000032:analysis / Q000172:deficiency / Q000235:genetics; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics; D012042:Registries; D050799:STAT5 Transcription Factor / Q000032:analysis
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters; D051858:Forkhead Transcription Factors; C098521:FOXF1 protein, human; D005819:Genetic Markers; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; C489679:SFTPC protein, human; D050799:STAT5 Transcription Factor