A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds

• Published in: The Journal of clinical investigation 1994-04, Vol.93 (4), p.1860-1863
• Main Authors: NOGEE, L. M, GARNIER, G, DIETZ, H. C, SINGER, L, MURPHY, A. M, DEMELLO, D. E, COLTEN, H. R
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Humans; Infant, Newborn; Medical sciences; Molecular Sequence Data; Mutation; Pneumology; Proteolipids - genetics; Pulmonary Alveolar Proteinosis - etiology; Pulmonary Alveolar Proteinosis - genetics; Pulmonary Surfactants - deficiency; Pulmonary Surfactants - genetics; Respiratory Distress Syndrome, Newborn - etiology; Respiratory system : syndromes and miscellaneous diseases; RNA Splicing
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci117173

To determine the molecular defect accounting for the deficiency of pulmonary surfactant protein B (SP-B) in full-term neonates who died from respiratory failure associated with alveolar proteinosis, the sequence of the SP-B transcript in affected infants was ascertained. A frameshift mutation consisting of a substitution of GAA for C in codon 121 of the SP-B cDNA was identified. The three affected infants in the index family were homozygous for this mutation, which segregated in a fashion consistent with autosomal recessive inheritance of disease. The same mutation was found in two other unrelated infants who died from alveolar 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 families and speculate that the disorder is more common than was recognized previously.