Pathogenesis and Natural History in a Longitudinal Hemangioma Syndrome Cohort

纵向血管瘤综合征队列的发病机制和自然史

• 批准号: 9038312
• 负责人: Dawn H. Siegel
• 金额: $ 35.67万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9038312
• 关键词: Accounting; Affect; Aortic coarctation; Bioinformatics; Biological Assay; Blood; Blood Vessels; Boxing; Brain; Cardiac; Caring; Cell Proliferation; Cellular biology; Cerebrovascular system; Characteristics; Childhood; Childhood stroke; Clinical; Congenital Abnormality; Congenital Hemangioma; Custom; DNA; Dandy-Walker Syndrome; Data; Defect; Dermatologist; Dermatology; Detection; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Endothelial Cells; Enrollment; Etiology; Eye; Eye Abnormalities; Face; Family; Fibroblasts; Foundations; Future; Genes; Genetic; Genetic Databases; Genomic DNA; Genomics; Genotype; Germ-Line Mutation; Goals; Head and neck structure; Health; Heart; Hemangioma; Hereditary Disease; High-Throughput Nucleotide Sequencing; In Vitro; Individual; Infant; Interdisciplinary Study; International; Knowledge; Medical Genetics; Medicine; Methods; Molecular; Morbidity - disease rate; Mosaicism; Mutation; Natural History; Newly Diagnosed; Online Systems; Outcome; Parents; Pathogenesis; Pathway interactions; Patient Care; Pediatric Neurology; Phenotype; Posterior Fossa; Pregnancy; Prevention strategy; Publishing; Recruitment Activity; Recurrence; Registries; Research; Research Personnel; Risk; Somatic Mutation; Source; Strawberry nevus; Stroke; Syndrome; System; Techniques; Technology; Therapeutic Agents; Tissues; Validation; Variant; adverse outcome; burden of illness; candidate validation; cell motility; cerebrovascular; clinical phenotype; cohort; design; developmental genetics; early childhood; exome sequencing; infancy; malformation; next generation; repository; single molecule; statistics

DESCRIPTION (provided by applicant): Background: PHACE syndrome is the association of large segmental facial hemangiomas and congenital birth defects, such as posterior fossa malformations. The vast majority of cases are sporadic, suggesting de novo or postzygotic somatic mutations may be the pathogenic mechanism. Gap: There is a fundamental lack of knowledge about the pathogenesis and natural history of the developmental anomalies in this hemangioma syndrome. Goal: Our primary objective is to elucidate the critical developmental genetic pathway involved in this hemangioma syndrome. Our secondary objective is to correlate the most severe clinical features (coarctation of the aorta, cerebrovascular anomalies and stroke) with the genotype. Aims: 1) We will use next generation high-throughput sequencing technology, custom designed analysis pipelines, and standard validation methods to identify mosaic mutations in PHACE. 2) We will capitalize on our rigorously phenotyped clinical PHACE registry and extensive preliminary data defining the clinical characteristics of PHACE syndrome to determine genotype-phenotype correlations. Significance: The contribution of the proposed research is expected to be an understanding of the genetic underpinnings of PHACE syndrome and phenotypic correlation with the associated developmental anomalies. This knowledge will be significant as it will drive strategies for prevention and provide critical targets for new therapeutic agents. Collaborators: Our multi-disciplinary study team includes expertise in dermatology (Siegel, Drolet and Frieden), medical genetics and child neurology (Dobyns), bioinformatics (Worthey), genomics (Worthey, Jacob and Shendure), statistics (Hoffman) and cell biology (Rafiee).

描述（由申请人提供）：

项目成果

Dental root abnormalities in four children with PHACE syndrome.

四名 PHACE 综合征儿童的牙根异常。

• DOI: 10.1111/pde.13818
• 发表时间: 2019
• 期刊: Pediatric dermatology
• 影响因子: 1.5
• 作者: Youssef,MollyJ;Siegel,DawnH;Chiu,YvonneE;Drolet,BethA;Hodgson,BrianD
• 通讯作者: Hodgson,BrianD

RNF213 variants in a child with PHACE syndrome and moyamoya vasculopathy.

患有 PHACE 综合征和烟雾病血管病的儿童中的 RNF213 变异。

• DOI: 10.1002/ajmg.a.38258
• 发表时间: 2017
• 期刊: American journal of medical genetics. Part A
• 作者: Schilter,KalaF;Steiner,JackE;Demos,Wendy;Maheshwari,Mohit;Prokop,JeremyW;Worthey,Elizabeth;Drolet,BethA;Siegel,DawnH
• 通讯作者: Siegel,DawnH

Evaluation of maternal history of miscarriage, infertility and in vitro fertilization as associated factors in PHACE.

评估母亲流产、不孕和体外受精史作为 PHACE 的相关因素。

• DOI: 10.1111/bjd.15341
• 发表时间: 2017
• 期刊: The British journal of dermatology
• 作者: Kim,ME;Cancel,M;Metry,D;Strawn,EY;Drolet,BA;Chiu,YE;Siegel,DH
• 通讯作者: Siegel,DH

Prenatal Risk Factors for PHACE Syndrome: A Study Using the PHACE Syndrome International Clinical Registry and Genetic Repository.

PHACE 综合征的产前危险因素：利用 PHACE 综合征国际临床注册和基因库进行的一项研究。

• DOI: 10.1016/j.jpeds.2017.06.055
• 发表时间: 2017
• 期刊: The Journal of pediatrics
• 作者: Wan,Joy;Steiner,Jack;Baselga,Eulalia;Blei,Francine;Cordisco,Maria;Garzon,MariaC;Goddard,DeborahS;Haggstrom,Anita;Krol,Alfons;Frieden,IlonaJ;Metry,Denise;Morel,KimberlyD;Verhagen,JudithMA;Wargon,Orli;Drolet,BethA;Siegel
• 通讯作者: Siegel

PHACE Syndrome: Consensus-Derived Diagnosis and Care Recommendations.

• DOI: 10.1016/j.jpeds.2016.07.054
• 发表时间: 2016-11
• 期刊: The Journal of pediatrics
• 作者: Garzon MC;Epstein LG;Heyer GL;Frommelt PC;Orbach DB;Baylis AL;Blei F;Burrows PE;Chamlin SL;Chun RH;Hess CP;Joachim S;Johnson K;Kim W;Liang MG;Maheshwari M;McCoy GN;Metry DW;Monrad PA;Pope E;Powell J;Shwayder TA;Siegel DH;Tollefson MM;Vadivelu S;Lew SM;Frieden IJ;Drolet BA
• 通讯作者: Drolet BA