RT Journal Article
SR Electronic
T1 Surfactant protein C G100S mutation causes familial pulmonary fibrosis in Japanese kindred
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP erj01436-2010
DO 10.1183/09031936.00143610
A1 S. Ono
A1 T. Tanaka
A1 M. Ishida
A1 A. Kinoshita
A1 J. Fukuoka
A1 M. Takaki
A1 N. Sakamoto
A1 Y. Ishimatsu
A1 S. Kohno
A1 T. Hayashi
A1 M. Senba
A1 M. Yasunami
A1 Y. Kubo
A1 L.M. Yoshida
A1 H. Kubo
A1 K. Ariyoshi
A1 K. Yoshiura
A1 K. Morimoto
YR 2011
UL http://erj.ersjournals.com/content/early/2011/08/04/09031936.00143610.abstract
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.