Basic and clinical immunologyDevelopment of population-based newborn screening for severe combined immunodeficiency
Section snippets
Samples
Blood samples from healthy adults and from infants newly diagnosed with SCID were donated with consent under approved research protocols at the National Institutes of Health. SCID molecular diagnosis was performed by sequencing IL2RG in male subjects as described16 and obtaining JAK3 sequence (GeneDx, Rockville, Md) where indicated. Umbilical cord blood was obtained from routine deliveries via the National Disease Research Interchange (Philadelphia, Pa). Simulated blood spots were made by
Results
Although simple to collect, dried blood spots vary widely in cellular content and extractable material, as illustrated by the 10-fold variation in DNA yields in our samples from 0.12 to 1.35 μg (mean, 0.46 μg) per 2 punches. Nonetheless, preliminary experiments showed significant positive correlations between TRECs and DNA content; β-actin copies and DNA content; and TRECs and β-actin copies (not shown). Multiple independent DNA preparations and PCR reactions were performed on a series of spots
Discussion
This study addresses previously unsatisfied criteria for newborn population screening for SCID: unavailability of incidence data and absence of an appropriate screening test. Paradoxically, the true incidence of SCID will be learned only through population screening. However, a minimum incidence can be estimated from our identification of 19 infants with XSCID mutations in a year and the annual US birthrate of 4,000,000.32 If blood from every XSCID infant born in the US were submitted to our
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Supported by National Human Genome Research Institute Division of Intramural Research, National Institutes of Health.