Newborn Screening for Sex Chromosome Disorders

DESCRIPTION (provided by applicant): Turner syndrome (TS) is the most common genetic problem effecting women, with an incidence of 1 in 1,500 to 2,000 live female births and occurs when an entire, or portions of an X-chromosome is deleted. Phenotypic features include primary hypogonadism, renal abnormalities, and profound short stature. Yet, with growth hormone therapy, acceptable adult stature can be achieved. Currently, many girls with TS are diagnosed after 10 years of age. Thus recognition of cardiac, renal, and learning problems may be delayed, and final height may be compromised. Girls with TS are also at risk for gonadal tumor development if Y-chromosomal is present. Recently we developed a strategy to screen for Tuner syndrome and other sex chromosome abnormalities that relies on genomic DNA screening using informative single nucleotide polymorphism (SNP) markers that span the X and Y-chromosomes. This is followed by quantitative assessment of allele, signal strength from single nucleotides via pyrosequencing. Thus, we propose to develop an effective, low-cost newborn screening test (the sex chromosome disorder screening test) for detecting TS with commercial application. Our Phasel milestones will be to (1) test for and optimize assay sensitivity and accuracy, (2) test for selectivity (rate of false-positives). (3) Create multiplex marker sets to minimize cost. We anticipate that this Phase 1 application will lead to the development of an assay that is suitable for high-throughput population screening for sex chromosome disorders. In next steps, we anticipate submitting a Phase 2 application for piloting large-scale newborn screening studies. If successful, this strategy will be applicable to the 2 million female infants born each year in the United States tested by state newborn screening programs, and to the several hundred thousand infants tested by commercial newborn screening services.