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 frameshift mutation (121ins2). Using independent clinical ascertainment and molecular methods in different populations, we sought to determine allele frequency.


METHODS
Using clinical characteristics of the phenotype of affected infants, we screened the Missouri linked birth-death database (n = 1 052 544) to ascertain potentially affected infants. We used molecular amplification and restriction enzyme digestion of DNA samples from a metropolitan New York birth cohort (n = 6599) to estimate allele frequency.


RESULTS
The point estimate and 95% confidence interval of the 121ins2 allele frequency in the Missouri cohort are 1/1000 individuals (.03-5.6/1000) and 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 suggests accurate gene frequency (approximately one 121ins2 mutation per 1000-3000 individuals) despite its rare occurrence and that this mutation does not account for the majority of full-term infants with lethal respiratory distress.
Cole
F S
FS
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St Louis Children's Hospital, St Louis, MO 63110, USA. cole@kids.wustl.edu
Hamvas
A
A
Rubinstein
P
P
King
E
E
Trusgnich
M
M
Nogee
L M
LM
deMello
D E
DE
Colten
H R
HR
D000483:Alleles; D005260:Female; D016368:Frameshift Mutation; D005787:Gene Frequency / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008923:Missouri / Q000453:epidemiology; D009518:New York / Q000453:epidemiology; D011510:Proteolipids / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000235:genetics*; D012127:Respiratory Distress Syndrome, Newborn / Q000453:epidemiology / Q000235:genetics*
D011510:Proteolipids; D011663:Pulmonary Surfactants