A MUTATION IN THE SURFACTANT PROTEIN-B GENE RESPONSIBLE FOR FATAL NEONATAL RESPIRATORY-DISEASE IN MULTIPLE KINDREDS

To determine the molecular defect accounting for the deficiency of pul monary surfactant protein B (SP-B) in full-term neonates who died from respiratory failure associated with alveolar proteinosis, the sequenc e of the SP-B transcript in affected infants was ascertained. A frames hift mutation consisting of a substitution of GAA for C in codon 121 o f the SP-B cDNA was identified. The three affected infants in the inde x family were homozygous for this mutation, which segregated in a fash ion consistent with autosomal recessive inheritance of disease. The sa me mutation was found in two other unrelated infants who died from alv eolar proteinosis, one of whom was also homozygous, and in the parents of an additional unrelated, affected infant, but was not observed in 50 control subjects. We conclude that this mutation is responsible for SP-B deficiency and neonatal alveolar proteinosis in multiple familie s and speculate that the disorder is more common than was recognized p reviously.