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，当整个或部分 X 染色体被删除时就会发生。 1,500 至 2,000 名活产女婴中 TS 1 的发病率。特征包括原发性性腺功能减退症、肾脏异常和心脏问题。患有 TS 的女孩身材矮小，成年平均身高为 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年身高。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被延迟。最终身高会因生长激素辅助治疗的迟发性而受到影响，如果从小开始进行辅助治疗，可以使患有 TS 的女孩达到正常的成年身高。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 染色体的信息性单核苷酸多态性 (SNP) 标记进行基因组 DNA 筛查。随后通过焦磷酸测序对等位基因信号强度和 SNP 数量进行定量评估。我们假设，利用这种新的性染色体筛查测试，我们可以开发出一种有效、低成本的筛查测试，用于检测 TS，并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所有报告的 TS 基因型。在该 SBIR 项目的第二阶段，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. 儿科内分泌诊所测试我们的测定。 (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. 进行新生儿筛查试验。 3. 制定测试和通知计划 我们预计这一二期应用将导致实施一种廉价的测试，该测试适合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 在 1,500 至 2,000 名活产女婴中发生，当整个或部分 X 染色体被删除时，就会发生 TS。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、肾脏和学习问题的识别可能会被延迟。最终身高会因生长激素辅助治疗的迟发性而受到影响，如果从小开始进行辅助治疗，可以使患有 TS 的女孩达到正常的成年身高。我们建议开发一种新的低成本筛选测试来检测具有广泛商业应用的 TS。