Original ArticleA common mutation in the surfactant protein C gene associated with lung disease
Section snippets
Patients and DNA
Patient samples were obtained as part of a collaborative study involving the Johns Hopkins Children's Center Hospital, St Louis Children's Hospital, and Cincinnati Children's Hospital to evaluate infants with lung disease of unknown cause for mutations in the surfactant protein genes. Samples were also recruited from physicians from other medical centers familiar with our work who were interested in having their patients evaluated for potential SP-B and SP-C gene abnormalities. The
Results
The I73T mutation was first identified by DNA sequence analysis of the SP-C gene in a 33-week-gestation female infant who initially presented with symptoms consistent with RDS but failed to wean off supplemental oxygen by 2 years of age. Evaluation was prompted when her mother was diagnosed with restrictive pneumonitis after delivery, and additional family history revealed an extensive familial lung disease kindred (Figure 1). A heterozygous thymine-to-cytosine transition was identified at
Discussion
We have identified a novel SP-C gene mutation, I73T, in multiple unrelated infants with lung disease. Although adult family members with the mutation who do not currently have lung disease were identified, incomplete penetrance has been recognized with another SP-C gene mutation with onset of lung disease in some individuals as late as the 6th decade.8 The segregation of the mutation with disease in the one extended kindred, the absence of the mutation in healthy control subjects, and the de
References (28)
- et al.
Surfactant protein deficiency in familial interstitial lung disease
J Pediatr
(2001) - et al.
Structural requirements for targeting of surfactant protein B (SP-B) to secretory granules in vitro and in vivo
J Biol Chem
(1996) - et al.
Mutations in the surfactant protein C gene associated with interstitial lung disease
Chest
(2002) - et al.
Mutation of a highly conserved isoleucine disrupts hydrophobic interactions in the alpha beta spectrin self-association binding site
Lab Invest
(2004) - et al.
Synthetic processing of surfactant protein C by alveolar epithelial cells: the COOH terminus of proSP-C is required for post-translational targeting and proteolysis
J Biol Chem
(1998) - et al.
Expression of a human surfactant protein C mutation associated with interstitial lung disease disrupts lung development in transgenic mice
J Biol Chem
(2003) - et al.
Pneumonitis and emphysema in sp-C gene targeted mice
J Biol Chem
(2003) - et al.
Two SP-C genes encoding human pulmonary surfactant proteolipid
J Biol Chem
(1988) - et al.
Hyaline membrane disease
Am Rev Respir Dis
(1975) - et al.
Importance of hydrophobic apoproteins as constituents of clinical exogenous surfactants
Am Rev Respir Dis
(1992)
Genetic disorders of neonatal respiratory function
Pediatr Res
Function of surfactant proteins B and C
Annu Rev Physiol
Allelic heterogeneity in hereditary surfactant protein B (SP-B) deficiency
Am J Respir Crit Care Med
A mutation in the surfactant protein C gene associated with familial interstitial lung disease
N Engl J Med
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Supported in part by grants from the National Institutes of Health [HL-54703 (L.M.N), HL-56387 (J.A.W., S.E.W., L.M.N.), HL-65174 (A.H.)], Forest Pharmaceuticals (H.S.C.), and the Eudowood Foundation.