Allelic heterogeneity in hereditary surfactant protein B (SP-B) deficiency

Lawrence M. Nogee, Susan E. Wert, Sherri A. Proffit, William M. Hull, Jeffrey A. Whitsett

Research output: Contribution to journalArticlepeer-review

184 Scopus citations


Inability to produce surfactant protein B (SP-B) causes fatal neonatal respiratory disease. A frameshift mutation (121ins2) is the predominant but not exclusive cause of disease. To determine the range of mechanisms responsible for SP-B deficiency, both alleles from 32 affected infants were characterized. Sixteen infants were homozygous for the 121ins2 mutation, 10 infants were heterozygous for the 121ins2 and another mutation, and six infants were homozygous for other mutations. Thirteen novel SP-B gene mutations were identified, which were not found in a control population. One novel mutation was found in two unrelated families. Surfactant protein expression was evaluated by immunohistochemistry and/or protein blotting. Absence of proSP-B and mature SP-B was associated with nonsense and frame- shift mutations. In contrast, proSP-B expresssion was associated with missense mutations, or mutations causing in-frame deletions or insertions, and low levels of mature SP-B expression were associated with four mutations. Extracellular staining for proSP-C and/or aberrantly processed SP-C was observed in lungs of all infants with SP-B gene mutations. Hereditary SP-B deficiency is caused by a variety of distinct mutations in the SP-B gene and may be associated with reduced, as well as absent, levels of mature SP-B, likely caused by impaired processing of proSP-B.

Original languageEnglish (US)
Pages (from-to)973-981
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Issue number3 I
StatePublished - 2000

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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