PT  - JOURNAL ARTICLE
AU  - S. Ono
AU  - T. Tanaka
AU  - M. Ishida
AU  - A. Kinoshita
AU  - J. Fukuoka
AU  - M. Takaki
AU  - N. Sakamoto
AU  - Y. Ishimatsu
AU  - S. Kohno
AU  - T. Hayashi
AU  - M. Senba
AU  - M. Yasunami
AU  - Y. Kubo
AU  - L.M. Yoshida
AU  - H. Kubo
AU  - K. Ariyoshi
AU  - K. Yoshiura
AU  - K. Morimoto
TI  - Surfactant protein C G100S mutation causes familial pulmonary fibrosis in Japanese kindred
AID  - 10.1183/09031936.00143610
DP  - 2011 Aug 04
TA  - European Respiratory Journal
PG  - erj01436-2010
4099  - http://erj.ersjournals.com/content/early/2011/08/04/09031936.00143610.short
4100  - http://erj.ersjournals.com/content/early/2011/08/04/09031936.00143610.full
AB  - Several mutations in surfactant protein C (SP-C) gene (SFTPC) have been reported as causing familial pulmonary fibrosis (FPF). However, the genetic background and clinical features of FPF are still not fully understood.We identified one Japanese kindred, in which at least six individuals over three generations were diagnosed with pulmonary fibrosis. We examined the patients radiologically and histopathologically and sequenced their SFTPC and ABCA3 genes. We also established a cell line stably expressing the mutant gene.All the patients had similar radiological and histopathological characteristics. Their histopathological feature was that of the usual interstitial pneumonia (UIP) pattern, showing numerous fibroblastic foci even in areas without abnormal radiological findings on chest HRCT. No child had respiratory symptoms in the kindred. Sequencing of SFTPC showed a novel heterozygous mutation, c.298G>A (G100S), in the BRICHOS domain of proSP-C, which co-segregated with the disease. Meanwhile in ABCA3 gene, no mutation was found. In vitro expression of the mutant gene revealed that several endoplasmic reticulum stress-related proteins were strongly expressed.Thus, the mutation increases endoplasmic reticulum stress and induces apoptotic cell death compared with wild-type SP-C in alveolar type II cells, supporting the significance of this mutation in the pathogenesis of pulmonary fibrosis.