CompoundSFTPB 1549C?GAA (121ins2) and 457delC heterozygosity in severe congenital lung disease and surfactant protein B (SP-B) deficiency

Surfactant proteins in pediatric interstitial lung disease

“…SP-B, a dimer of 16 kDa, was detected easily in all cases investigated except for the single case of hereditary SP-B deficiency. Together with the finding of lacking SP-B in all other reported cases of this genetic disorder (7,17,18,(24)(25)(26) and the successful rescue of SP-B-deficient knockout mice (27), the analysis of BALF for SP-B concentration appears diagnostically helpful when pediatric DPLD potentially including this rare condition are investigated. In this context, it must be recommended to sample BAL before exogenous surfactant is applied, as the latter usually contains both SP-B and SP-C whose in vivo half-lives may be very long (28)(29)(30).…”

“…In particular, no studies have compared the full range of these diseases, to yield better estimates of variability and to examine the relative importance of biochemical determinations of their BALF levels. It has been shown that the levels of SP-C in patients with known mutations in SFTPB (17,18), SFTPC (19,20), ABCA3 (21), and TTF1 (22) are low. Thus, we hypothesized that SP-C might serve as a helpful screening tool for such and additional surfactant dysfunction disorders.…”

Multilayer Formation upon Compression of Surfactant Monolayers Depends on Protein Concentration as Well as Lipid Composition

“…In an effort to circumvent the possibility of zoonotic infections and to reduce the considerable costs of surfactant production, the use of surfactants containing artificial proteins and lipids is currently under consideration. With respect to the proteins, the hydrophobic surfactant protein B (SP-B) is known to fulfill a crucial role in the lung since respiratory distress is always observed in SP-Bdeficient humans (13,14) and in homozygous SP-B-knockout mice (15). SP-B is a 79-amino acid amphipathic protein active as an 18-kDa dimer (16) and has a net positive charge that is thought to be essential for its interaction with negatively charged phospholipids such as phosphatidylglycerol (PG) (17)(18)(19).…”

Paediatric interstitial lung disease

“…A number of mutations have been described, the commonest being a frameshift mutation in exon 4 (1549C➞GAA, 121ins2), but also 122delC [46], 457delC [47] and other mutations listed in [48]. The mutation frequency in the population is probably 1 per 1-3,000 individuals [49].…”