Population-based estimates of surfactant protein B deficiency

Objective. Surfactant protein B deficiency is a lethal cause of respiratory distress in infancy that results most commonly from a homozygous frameshif t mutation (121ins2). Using independent clinical ascertainment and molecula r methods in different populations, we sought to determine allele frequency . Study Design. Using clinical characteristics of the phenotype of affected i nfants, we screened the Missouri linked birth-death database (n = 1 052 544 ) to ascertain potentially affected infants. We used molecular amplificatio n and restriction enzyme digestion of DNA samples from a metropolitan New Y ork birth cohort (n = 6599) to estimate allele frequency. Results. The point estimate and 95% confidence interval of the 121ins2 alle le frequency in the Missouri cohort are 1/1000 individuals (.03-5.6/1000) a nd in the New York cohort are .15/1000 (.08-.25/1000). These estimates are not statistically different. Conclusions. The close approximation of these independent estimates suggest s accurate gene frequency (approximately one 121ins2 mutation per 1000-3000 individuals) despite its rare occurrence and that this mutation does not a ccount for the majority of full-term infants with lethal respiratory distre ss.