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.


OBJECTIVE
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.
Department of neonatology, Academic Medical Center, Amsterdam, The Netherlands.
F A B A
FA
Schuerman
M
M
Griese
J P
JP
Gille
F
F
Brasch
L A
LA
Noorduyn
A H
AH
van Kaam
D001706:Biopsy; D004247:DNA / Q000378:metabolism; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008954:Models, Biological; D009154:Mutation; D011498:Protein Precursors / Q000172:deficiency* / Q000235:genetics*; D011510:Proteolipids / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013501:Surface-Active Agents / Q000378:metabolism; D014132:Trachea / Q000378:metabolism
D011498:Protein Precursors; D011510:Proteolipids; D013501:Surface-Active Agents; C105511:surfactant protein B propeptide; D004247:DNA