Surfactant protein B deficiency caused by a novel mutation involving multiple exons of the SP-B gene.

BACKGROUND: Inability to produce surfactant protein (SP)-B causes fatal neonatal respiratory disease. Homozygosity for a frameshift mutation (121ins2) in the gene encoding SP-B (SFTPB) is the predominant but not the exclusive cause of disease. OBJECTIVES: To report a novel mutation in the SFTB gene. METHODS: We analyzed tracheal aspirates, lung tissue obtained by in vivo lung biopsy and DNA from a newborn infant with lethal respiratory failure. RESULTS: DNA analysis revealed a large homozygous genomic deletion encompassing exon 7 and 8 of SFTPB gene, a mutation we described as c.673-1248del2959. The parents were both heterozygous carriers. Analysis of the SP profile in tracheal aspirates and lung tissue by immunohistochemistry, routine and electron microscopy supported the diagnosis of SP-B deficiency and suggested that this large mutation might lead to abnormal routing and processing of proSP-B and proSP-C. CONCLUSIONS: This report shows that SP-B deficiency can also be caused by a multi exon deletion in the SFTPB gene and this finding emphasizes the importance of using modern DNA analysis techniques capable of detecting multi exon deletions.