Newborn Screening for Sex Chromosome Disorders

新生儿性染色体疾病筛查

• 批准号: 7218361
• 负责人: SEIYU HOSONO
• 金额: $ 48.85万
• 依托单位: JS GENETICS, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7218361
• 关键词: Adult; Affect; Age; Age-Years; Alleles; Biological Assay; Birth; Cardiac; Cell Line; Childhood; Chromosome Deletion; Clinic; Clinical Trials; Complex; Congenital Heart Defects; DNA; Detection; Development; Diagnosis; Diagnostic tests; Early Diagnosis; Endocrinologist; Endocrinology; Estrogens; Ethnic group; Failure; Female; Genetic; Genomics; Genotype; Height; Incidence; Karyotype; Kidney; Klinefelter' s Syndrome; Laboratories; Lead; Learning; Life; Mosaicism; Neonatal Screening; Neurologic Manifestations; Notification; Numbers; Phase; Phase I Clinical Trials; Physicians; Population; Progestins; Race; Rate; Reaction; Replacement Therapy; Reporting; Risk; Sampling; Screening procedure; Sex Chromosome Aberrations; Sex Chromosome Disorders; Sex Chromosomes; Signal Transduction; Single Nucleotide Polymorphism; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Somatotropin; Space Perception; Standards of Weights and Measures; Testing; Turner' s Syndrome; Woman; X Chromosome; Y Chromosome; base; commercial application; cost; foot; girls; high throughput screening; hormone therapy; pediatrician; programs; tumor

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.

描述（由申请人提供）：特纳综合征（TS）是影响女性的最常见遗传问题，当整个X染色体的一部分或一部分被删除时发生。 1,500至2,000名活着的女性出生中Ts 1的发病率。特征包括主要的性腺功能减退，肾脏异常和心脏问题。 TS的女孩短，成人平均身高为4英尺6英寸。然而，通过生长激素疗法，可以实现可接受的成人身材。目前，许多有TS的女孩在10岁以后被诊断出。因此，可能会延迟对相关心脏，肾脏和其他问题的认识。最终的高度将因生长激素的辅助治疗晚期损害，如果从早期开始，则允许具有TS的女孩达到正常的成人身高。最近，我们制定了一种检测TS和其他性别染色体异常的策略，该策略依赖于使用跨越X-和Y染色体的信息单核苷酸多态性（SNP）标记来筛选基因组DNA筛选。接下来是对等位基因信号强度和SNP的数量进行定量评估。我们假设使用这种新的性染色体筛选测试，我们可以开发有效的低成本筛选测试，以检测具有广泛商业应用的TS。为了优化这种方法，以高灵敏度以最低的成本进行高通量筛查，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TS的所有报告的基因型。在该SBIR项目的第二阶段中，我们建议将诊断测试扩展到临床试验并制定测试和推荐计划。我们将在1。小儿内分泌诊所测定我们的测定法。 （a）来自已知有TS的女孩的测试样本。 （b）身材矮小的女孩的测试样品。 2。执行新生儿筛查试验。 3。制定测试和通知程序，我们预计该II期应用将导致实施廉价测试，该测试适合于医生和新生儿筛查计划检测性染色体疾病。特纳综合征（TS）是影响女性的最常见遗传问题。 Ts 1中的1,500至2,000名活着的女性出生的发生率是在删除整个X染色体或一部分X染色体时发生的。目前，许多有TS的女孩在10岁以后被诊断出。因此，可能会延迟对相关心脏，肾脏和学习问题的认识。最终的高度将因生长激素的辅助治疗晚期损害，如果从早期开始，则允许具有TS的女孩达到正常的成人身高。我们建议开发一种新的低成本筛查测试，以检测具有广泛商业应用的TS。