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.
Schuerman
F A B A
FA
Department of neonatology, Academic Medical Center, Amsterdam, The Netherlands.
Griese
M
M
Gille
J P
JP
Brasch
F
F
Noorduyn
L A
LA
van Kaam
A H
AH
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