Molecular and phenotypic variability in the congenital alveolar proteinosis syndrome associated with inherited surfactant protein B deficiency

Daphne E. deMello, Lawrence M. Nogee, Sarah Heyman, Henry F. Krous, Mukarram Hussain, T. Allen Merritt, Wei Hsueh, Joel E. Haas, Kathleen Heidelberger, Robert Schumacher, Harvey R. Colten

Research output: Contribution to journalArticlepeer-review

Abstract

Congenital alveolar proteinosis (CAP) is an often fatal cause of respiratory failure in term newborn infants, which has been associated with a genetic deficiency of surfactant protein B (SP-B) as a result of a frameshift mutation (121ins2) in a family with three affected siblings. In the index cases the deficiency of SP-B was associated with qualitative and quantitative abnormalities of the surfactant proteins A and C. Immunostaining for lung surfactant proteins and a search for the 121ins2 mutation by restriction enzyme analysis of DNA extracted from paraffin-embedded lung tissue was performed for 7 additional affected infants from 6 families, bringing to 10 the total number of patients with CAP who have been studied. In six infants, the surfactant protein immunostaining pattern was similar to that of the index cases. Of these, three patients were homozygous for the 121ins2 mutation; one was a compound heterozygote with the 121ins2 in one allele and a different mutation in the other; and three patients lacked the mutation in both alleles. One infant had an abundance of SP-B, suggesting phenotypic heterogeneity in CAP. Lung ultrastructural abnormalities, such as a reduced number of lamellar bodies, absent tubular myelin, and basal secretion of surfactant lipids and proteins, suggest a significant derangement of surfactant metabolism. The phenotypic heterogeneity in infants with CAP raises the possibility that variable degrees of SP-B deficiency may be more common than previously suspected. (J PEDIATR 1994;125:43-50)

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalJournal of Pediatrics
Volume125
Issue number1
DOIs
StatePublished - 1994
Externally publishedYes

Keywords

  • CAP
  • Congenital alveolar proteinosis
  • SP-A
  • SP-B
  • SP-C
  • Surfactant protein A
  • Surfactant protein B
  • Surfactant protein C

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Fingerprint Dive into the research topics of 'Molecular and phenotypic variability in the congenital alveolar proteinosis syndrome associated with inherited surfactant protein B deficiency'. Together they form a unique fingerprint.

Cite this