A multidisciplinary approach for identifying and characterizing novel congenital malformation syndromes
识别和表征新型先天畸形综合征的多学科方法
基本信息
- 批准号:9977879
- 负责人:
- 金额:$ 40.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-25 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAffectBig DataBiological AssayBirthCase StudyCatalogsChildChildhoodClinicClinicalCongenital AbnormalityDNADataDiagnosisDisease ProgressionEpidemiologistEtiologyEvaluationFamilyFoundationsGeneticGenetic CounselingGenetic Predisposition to DiseaseGoalsHealthIndividualInfantInternationalLeadLiteratureLive BirthLysosomal Storage DiseasesMedicalMedical GeneticsMethodsNucleotidesOrphanOrphan DrugsOutcomeParentsPathway interactionsPatientsPatternPhenotypePopulationPreventionPublic HealthRare DiseasesRecurrenceRegistriesReportingResearchReview LiteratureSamplingSchemeStructureSyndromeVariantbaseclinically significantcomparative genomic hybridizationcostdata registryde novo mutationexome sequencingexpectationexperiencegenetic testingimprovedinterdisciplinary approachmalformationnovelnovel therapeuticsoutcome forecastpopulation basedpreventprogramsrare conditionrecruitreproductivesuccesstargeted biomarkertherapeutic targettherapy development
项目摘要
Over 50% of children with multiple malformations seen in medical genetics clinics for a
suspected genetic syndrome never receive a diagnosis, which leaves unanswered questions
about prognosis and medical/reproductive planning. While individual multiple malformation
syndromes (MMS) are rare diseases (many <1 in 200,000 births), in combination, these
conditions are costly and medically severe. There have been some recent successes in
developing orphan treatments for some of these rare syndromes, but this only represents the
“tip of the iceberg,” and it is thought that there are many more recognized and unrecognized
MMS that will be amenable to new therapies. The next steps toward identifying therapeutic
targets and biomarkers of outcomes for these rare diseases are to 1) identify these MMS, 2)
characterize their clinical profile, and 3) uncover the underlying genetic causes. To accomplish
these goals, we will first identify “new” MMS (i.e., not described in the literature) using
international data from two large networks that represent most of the major birth defects
registries worldwide. By leveraging these population-based data, we will address the limitations
of previous approaches for identifying new MMS (i.e., clinical case reports based on a small
number of cases identified in a single clinic). Second, we will verify the occurrence of
“unconfirmed” MMS (i.e., unconfirmed case reports of only a few cases) using our international
network of birth defects registries to address the possibility that that the malformations patterns
reported in these previous case reports occurred due to chance alone. We will use a network of
medical genetics clinics we have assembled to recruit clinical patients with the new MMS and
the unconfirmed MMS that we validate. We will conduct systematic phenotyping of these cases
to better delineate the clinical profiles of these syndromes. We will also collect DNA samples
from these patients and their families and conduct exome sequencing, which may identify
pathways that could lead to therapeutic targets for these rare but clinically significant conditions.
超过 50% 的多发畸形儿童在医学遗传学诊所就诊
疑似遗传综合症从未得到诊断,这留下了悬而未决的问题
关于个体多发畸形的预后和医疗/生殖计划。
综合征 (MMS) 是一种罕见疾病(许多人在 200,000 名新生儿中<1),综合起来,这些
条件昂贵且医疗条件严峻,最近在这方面取得了一些成功。
正在开发针对其中一些罕见综合征的孤儿疗法,但这仅代表
“冰山一角”,人们认为还有更多已被认可和未被认可的
MMS 将适合新疗法的下一步确定治疗方法。
这些罕见疾病结果的目标和生物标志物是 1) 识别这些 MMS,2)
描述他们的临床特征,3) 揭示潜在的遗传原因。
这些目标,我们将首先使用以下方法确定“新”MMS(即文献中未描述的)
来自代表大多数主要出生缺陷的两个大型网络的国际数据
通过利用这些基于人口的数据,我们将解决这些限制。
以前用于识别新 MMS 的方法(即基于小型的临床病例报告)
其次,我们将验证是否发生
“未经证实的”MMS(即仅少数病例的未经证实的病例报告)使用我们的国际
出生缺陷登记网络,以解决畸形模式的可能性
先前的案例报告中所报道的情况纯属偶然,我们将使用网络。
我们组建了医学遗传学诊所,用新的 MMS 招募临床患者,
我们将对这些病例进行系统表型分析。
为了更好地描述这些综合征的临床特征,我们还将收集 DNA 样本。
从这些患者及其家人身上进行外显子组测序,这可能会识别出
可能导致这些罕见但具有临床意义的疾病的治疗靶点的途径。
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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A.J. Agopian其他文献
A.J. Agopian的其他文献
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{{ truncateString('A.J. Agopian', 18)}}的其他基金
A multidisciplinary approach for identifying and characterizing novel congenital malformation syndromes
识别和表征新型先天畸形综合征的多学科方法
- 批准号:
10443745 - 财政年份:2018
- 资助金额:
$ 40.19万 - 项目类别:
A multidisciplinary approach for identifying and characterizing novel congenital malformation syndromes
识别和表征新型先天畸形综合征的多学科方法
- 批准号:
9769104 - 财政年份:2018
- 资助金额:
$ 40.19万 - 项目类别:
Do Cesarean Deliveries Reduce Mortality in Infants with Birth Defects?
剖腹产会降低出生缺陷婴儿的死亡率吗?
- 批准号:
9175062 - 财政年份:2016
- 资助金额:
$ 40.19万 - 项目类别:
Do Cesarean Deliveries Reduce Mortality in Infants with Birth Defects?
剖腹产会降低出生缺陷婴儿的死亡率吗?
- 批准号:
9333411 - 财政年份:2016
- 资助金额:
$ 40.19万 - 项目类别:
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