Newborn Screening for Sex Chromosome Disorders

描述（由申请人提供）：特纳综合征（TS）是影响女性的最常见的遗传问题，当整个或部分x染色体被删除时发生。每1 500至2 000名活产女婴中有1型TS的发病率。其特征包括原发性性腺功能减退、肾脏异常和心脏问题。患有TS的女孩身材矮小，成年后的平均身高为4英尺6英寸。然而，通过生长激素治疗，可以达到可接受的成人身材。目前，许多患有TS的女孩在10岁后被诊断出来。因此，对相关心脏、肾脏和其他问题的识别可能会延迟。最终的身高将受到生长激素的晚发性辅助治疗的影响，如果在早期开始，TS女孩可以达到正常的成人身高。最近，我们开发了一种检测TS和其他性染色体异常的策略，该策略依赖于使用跨越X和y染色体的信息丰富的单核苷酸多态性（SNP）标记进行基因组DNA筛选。随后通过焦磷酸测序对snp的等位基因信号强度和数量进行定量评估。我们假设，利用这种新的性染色体筛选试验，我们可以开发出一种有效的、低成本的检测TS的筛选试验，具有广泛的商业应用。为了以尽可能低的成本和高灵敏度优化这种高通量筛选方法，我们最近完成了非常成功的I期研究，并表明我们可以检测到所有已报道的TS基因型。在这个SBIR项目的II期，我们建议将我们的诊断测试扩展到临床试验，并制定测试和转诊计划。我们将在1号进行试验。儿科内分泌科诊所。(a)已知患有TS的女孩的测试样本。(b)身材矮小的女孩的测试样本。2. 开展新生儿筛查试验。和3。开发测试和通知程序我们预计，这个第二阶段的申请将导致实施一种廉价的测试，适用于医生和新生儿筛查项目检测性染色体疾病。特纳综合症（TS）是影响女性的最常见的遗传问题。TS - 1的发病率在1500到2000名活产的女性中，当x染色体的整个或部分被删除时，TS就会发生。目前，许多患有TS的女孩在10岁后被诊断出来。因此，对相关的心脏、肾脏和学习问题的识别可能会延迟。最终的身高将受到生长激素的晚发性辅助治疗的影响，如果在早期开始，TS女孩可以达到正常的成人身高。我们建议开发一种新的低成本筛选试验，以检测具有广泛商业应用的TS。

DESCRIPTION (provided by applicant): Turner syndrome (TS) is the most common genetic problem affecting women and occurs when an entire, or a portion of an X-chromosome is deleted. The incidence of TS 1 in 1,500 to 2,000 live female births. Features include primary hypogonadism, renal abnormalities and cardiac problems. Girls with TS are short and have an average adult height of 4 feet 6 inches. 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 associated cardiac, renal, and other problems may be delayed. Final height will be compromised by late-onset of adjunctive therapy with growth hormone, which if begun at an early age, allows girls with TS to achieve normal adult height. Recently, we developed a strategy to detect TS and other sex chromosome abnormalities that relies on genomic DNA screening using informative single nucleotide polymorphism (SNP) markers spanning the X- and Y-chromosomes. This is followed by quantitative assessment of allele signal strength and number from SNPs via pyrosequencing. We hypothesize that using this new sex chromosome screening test we can develop an effective, low-cost screening test for detecting TS with broad commercial application. To optimize this approach for high-throughput screening at the lowest possible cost with high sensitivity, we recently completed Phase I studies that were highly successful, and show that we can detect ALL of the reported genotypes of TS. In Phase II of this SBIR project, we propose to extend our diagnostic test to clinical trials and develop a testing and referral program. We will test our assay in 1. Pediatric Endocrinology Clinics. (a) Test samples from girls known to have TS. (b) Test samples from girls with short stature. 2. Perform Newborn Screening Trials. and 3. Develop Testing and Notification Programs We anticipate that this Phase II application will lead to implementation of an inexpensive test that is suitable for detection of sex chromosome disorders by physicians and newborn screening programs. Turner syndrome (TS) is the most common genetic problem affecting women. The incidence of TS 1 in 1,500 to 2,000 live female births, and TS occurs when an entire, or a portion of an X-chromosome is deleted. Currently, many girls with TS are diagnosed after 10 years of age. Thus recognition of associated cardiac, renal, and learning problems may be delayed. Final height will be compromised by late-onset of adjunctive therapy with growth hormone, which if begun at an early age, allows girls with TS to achieve normal adult height. We propose the development of a new low-cost screening test for detecting TS with broad commercial application.