Hereditary interstitial lung diseases manifesting in early childhood in Japan

Pediatr Res. 2014 Nov;76(5):453-8. doi: 10.1038/pr.2014.114. Epub 2014 Aug 8.


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.

Conclusion: The SP-C abnormality was most prevalent, and SP-B deficiency was rare in Japanese infants with hereditary ILD.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Age of Onset
  • Asians / genetics
  • Female
  • Forkhead Transcription Factors / genetics
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Heredity
  • Humans
  • Infant
  • Infant, Newborn
  • Japan / epidemiology
  • Leukocytes, Mononuclear / chemistry
  • Lung Diseases, Interstitial / diagnosis
  • Lung Diseases, Interstitial / ethnology
  • Lung Diseases, Interstitial / genetics*
  • Lung Diseases, Interstitial / physiopathology
  • Lung Diseases, Interstitial / therapy
  • Male
  • Phenotype
  • Phosphorylation
  • Pulmonary Alveolar Proteinosis / congenital
  • Pulmonary Alveolar Proteinosis / ethnology
  • Pulmonary Alveolar Proteinosis / genetics
  • Pulmonary Surfactant-Associated Protein B / analysis
  • Pulmonary Surfactant-Associated Protein B / deficiency
  • Pulmonary Surfactant-Associated Protein B / genetics
  • Pulmonary Surfactant-Associated Protein C / genetics
  • Registries
  • STAT5 Transcription Factor / analysis


  • ABCA3 protein, human
  • ATP-Binding Cassette Transporters
  • FOXF1 protein, human
  • Forkhead Transcription Factors
  • Genetic Markers
  • Pulmonary Surfactant-Associated Protein B
  • Pulmonary Surfactant-Associated Protein C
  • SFTPC protein, human
  • STAT5 Transcription Factor

Supplementary concepts

  • Congenital Deficiency of Pulmonary Surfactant Protein B