Aberrant SP-B mRNA in lung tissue of patients with congenital alveolar proteinosis (CAP)

Mutations in the surfactant protein (SP)-B gene are responsible for SP-B de ficiency in congenital alveolar proteinosis (CAP) (Nogee et al. J Clin Inve st 1994: 93: 1860-1883; Lin et al. Mol Genet Metab 1998. 64: 25-35; Klein e t al, Pediatrics 1998: 132: 244-248; Ballard et al. Pediatrics 1995: 96: 10 46-1052). The multigenerational consanguineous pedigree under study does no t carry any of the known mutations, although this pedigree had 14 infant de aths following respiratory distress at birth. Immunostaining of the lungs f rom three such infants revealed decreased or absent SP-B. By sequencing of SP-B exons, exon-intron junctions, and the 5' and 3' flanking regions, nine polymorphisms were found in this pedigree, but none of them could explain the observed SP-B deficiency. Further analysis of SP-B mRNA by reverse tran scription-polymerase chain reaction from paraffin-embedded lung tissue of C AP patients showed that SP-B mRNA is not intact. Although the sequence of m RNA from exon 1-exon 7 and from exon 8-exon 10 could be amplified, the regi on between exons 7 and 8 could not. From fluorescence in situ hybridization of the short arm of chromosome 2p, only 2 signals were identified, elimina ting the possibility of translocation as the cause of the SP-B mRNA aberran ce, Although the nature of the genetic basis of SP-B deficiency in this fam ily is currently unknown, the existence of aberrant SP-B mRNA may, at least in part, be responsible for the SP-B deficiency in this pedigree.