PURPOSE: Idiopathic interstitial pneumonias (IIPs) are one of a large number of diffuse parenchymal lung diseases characterized by parenchymal inflammation and fibrosis without any known cause. Recently, mutations in SFTPC were reported to be identified in patients with familial IP. Based on this knowledge, we tried to identify mutation in SFTPC in patients with IIPs and evaluated the clinical characteristics of these patients.
METHODS: We enrolled 104patients with interstitial pneumonia (IP), which were composed of 29 patients with familial IP (child-onset n= 2; adult-onset n=27) and 75 patients with sporadic IP (child-onset n=36; adult-onset n=40), and 50 healthy volunteers. Diagnosis was determined by either radiography or histopathology. Sequencing of SFTPC locus was performed in DNA extracted from blood.
RESULTS: We identified fifteen heterozygous missense mutations in SFTPC, containing twelve novel mutations (six in exon 2, five in exon3, one in exon5) and the deletion of exon4, and two well-known mutations in exon 3.Mutations of SFTPC in sporadic IP were identified in 36% (n=13) of child-onset IP, but not adult-onset IP. In contrast, mutations of SFTPC in familial IP were detected in both adult-onset IP(15%) and child-onset IP (100%). Either familial or sporadic IP was associated with high frequency of mutation of SFTPC in child-onset IP (39%) compared to adult-onset IP (6%). Interestingly, over a half of cases with mjutation in exon2 in child-onset IP were associated with pulmonary alveolar proteinosis.
CONCLUSIONS: This data indicated that at least child-onset IP or familial IP could be linked to mutation of SFTPC.
CLINICAL IMPLICATIONS: This study provides evidence that mutation in SFTPC could play a important role in development of IP.
DISCLOSURE: Yasuhiro Setoguchi: Grant monies (from sources other than industry): Government
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