SFTPC deficiency

Dominant mutations in the surfactant protein-C(SFTPC) gene have been linked with interstitial lung disease. The frequency of lung disease due to SFTPC mutations in the general population is unknown.

SFTPC mutations are a frequent cause of pediatric diffuse lung diseases.

The SFTPC gene encodes pulmonary-associated surfactant protein C (SP-C), an extremely hydrophobic surfactant protein essential for lung function and homeostasis after birth. SP-C is produced exclusively by type II alveolar epithelial cells in the lung.

Pulmonary surfactant is a lipid-rich material that prevents lung collapse by lowering surface tension at the air-liquid interface in the alveoli of lung. Surfactant is composed of phospholipids and other surfactant-associated proteins (Clark and Clark, 2005). See also SFTPA1 (178630), SFTPB (178640), and SFTPD (178635).

Synopsis

Types

 SFTPC-associated idiopathic interstitial pneumonias (17005585)
 SFTPC-associated common paediatric lung diseases (17121584)
 SFTPC-associated increased susceptibility to infection (16449190)
 SFTPC-associated neonatal respiratory failure (16355106)
 SFTPC-associated infantile interstitial lung disease (15293602)
 SFTPC-associated familial interstitial lung disease (11207353)
 SFTPC-associated early interstitial lung disease (20371530)
 SFTPC-associated infantile pulmonary alveolar proteinosis with or without fibrosing lung disease (15039969)

Some heterozygotes for the mutations have normal lung function and are unaffected by COPD and interstitial lung disease. (19910179)

Mutations

 I73T mutation is the most frequent SFTPC mutation associated with diffuse lung disease.

 Mutations are located in the BRICHOS domain except the p.Val39Ala (V39A) mutation, which is in the surfactant protein C (SP-C) mature peptide.

Predisposition

 A53T heterozygotes have increased asthma risk. (19910179)

See also

 pulmonary surfactant
 surfactant proteins
 SFTPB-deficiency

References

 Identification of early interstitial lung disease in an individual with genetic variations in ABCA3 and SFTPC. Crossno PF, Polosukhin VV, Blackwell TS, Johnson JE, Markin C, Moore PE, Worrell JA, Stahlman MT, Phillips JA 3rd, Loyd JE, Cogan JD, Lawson WE. Chest. 2010 Apr;137(4):969-73. PMID: 20371530

 New surfactant protein C gene mutations associated with diffuse lung disease. Guillot L, Epaud R, Thouvenin G, Jonard L, Mohsni A, Couderc R, Counil F, de Blic J, Taam RA, Le Bourgeois M, Reix P, Flamein F, Clement A, Feldmann D. J Med Genet. 2009 Jul;46(7):490-4. PMID: 19443464 (Free)

 Two novel mutations in surfactant protein-C, lung function and obstructive lung disease. Bækvad-Hansen M, Nordestgaard BG, Tybjærg-Hansen A, Dahl M. Respir Med. 2009 Nov 10. PMID: 19910179

 Markart P, Ruppert C, Wygrecka M, Schmidt R, Korfei M, Harbach H, Theruvath I, Pison U, Seeger W, Guenther A, Witt H. Surfactant protein C mutations in sporadic forms of idiopathic interstitial pneumonias. Eur Respir J. 2007 Jan;29(1):134-7. PMID: 17005585

 Puthothu B, Krueger M, Heinze J, Forster J, Heinzmann A. Haplotypes of surfactant protein C are associated with common paediatric lung diseases. Pediatr Allergy Immunol. 2006 Dec;17(8):572-7. PMID: 17121584

 Nogee LM. Genetics of pediatric interstitial lung disease. Curr Opin Pediatr. 2006 Jun;18(3):287-92. PMID: 16721150

 Bridges JP, Xu Y, Na CL, Wong HR, Weaver TE. Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-C. J Cell Biol. 2006 Jan 30;172(3):395-407. PMID: 16449190

 Soraisham AS, Tierney AJ, Amin HJ. Neonatal respiratory failure associated with mutation in the surfactant protein C gene. J Perinatol. 2006 Jan 1;26(1):67-70. PMID: 16355106

 Tredano M, Griese M, Brasch F, Schumacher S, de Blic J, Marque S, Houdayer C, Elion J, Couderc R, Bahuau M. Mutation of SFTPC in infantile pulmonary alveolar proteinosis with or without fibrosing lung disease. Am J Med Genet A. 2004 Apr 1;126(1):18-26. PMID: 15039969

 Brasch F, Griese M, Tredano M, Johnen G, Ochs M, Rieger C, Mulugeta S, Muller KM, Bahuau M, Beers MF. Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene. Eur Respir J. 2004 Jul;24(1):30-9. PMID: 15293602

 Analysis of 40 sporadic or familial neonatal and pediatric cases with severe unexplained respiratory distress: relationship to SFTPB. Tredano M, Griese M, de Blic J, Lorant T, Houdayer C, Schumacher S, Cartault F, Capron F, Boccon-Gibod L, Lacaze-Masmonteil T, Renolleau S, Delaisi B, Elion J, Couderc R, Bahuau M. Am J Med Genet A. 2003 Jun 15;119A(3):324-39. PMID: 12784301

 Nogee LM, Dunbar AE 3rd, Wert SE, Askin F, Hamvas A, Whitsett JA. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med. 2001 Feb 22;344(8):573-9. PMID: 11207353