PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation.
PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation.
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与PIK3CA相关的过度生长光谱（专业）：诊断和测试资格标准，差异诊断和评估。
DOI：
10.1002/ajmg.a.36836
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发表时间：
2015-02
影响因子：
2
通讯作者：
Biesecker, Leslie G.
中科院分区：
文献类型：
--
作者：
Keppler-Noreuil, Kim M.;Rios, Jonathan J.;Parker, Victoria E. R.;Semple, Robert K.;Lindhurst, Marjorie J.;Sapp, Julie C.;Alomari, Ahmad;Ezaki, Marybeth;Dobyns, William;Biesecker, Leslie G.
关键词：
磷脂酰肌醇-3-激酶/AKT/mTOR通路中的体细胞激活突变是异质节段性过度生长表型的基础。由于患者之间的极端差异，我们试图描述与不同基因型和突变负荷相关的表型谱，包括更好地了解相关并发症和自然史。历史上，患有PIK 3CA激活突变的患者的临床诊断包括纤维脂肪增生或过度生长（FAO）、半增生性多发性脂肪瘤病（HHML）、先天性脂肪瘤过度生长、血管畸形、表皮痣、脊柱侧凸/骨骼和脊柱（CLOVES）综合征、巨指畸形、纤维脂肪浸润性脂肪瘤病和相关的巨脑畸形综合征，巨脑毛细血管畸形（MCAP或M-CM）和发育不良性巨脑畸形（DMEG）。在美国国立卫生研究院（NIH）召开了一次研讨会，讨论并制定了一份关于诊断和治疗PIK 3CA相关躯体过度生长障碍患者的共识文件。研讨会的与会者包括来自几个机构的研究人员，他们一直在研究这些疾病并发表了他们的研究结果，以及来自患者倡导和支持团体的代表。一致同意“PIK 3CA相关过度生长谱（PROS）”的总括术语涵盖与体细胞PIK 3CA突变相关的已知和新出现的临床实体，包括巨指畸形、FAO、HHML、CLOVES和相关的巨脑畸形病症。提出了关键的临床诊断特征和检测标准，并总结了检测方法。初步建议，一个统一的方法来评估过度生长和分子诊断测试确定。未来需要解决的领域包括过度生长组织和血管异常的外科治疗，血栓形成风险的最佳方法，以及潜在药物治疗的测试。
Somatic activating mutations in the phosphatidylinositol-3-kinase/AKT/mTOR pathway underlie heterogeneous segmental overgrowth phenotypes. Because of the extreme differences among patients, we sought to characterize the phenotypic spectrum associated with different genotypes and mutation burdens, including a better understanding of associated complications and natural history. Historically, the clinical diagnoses in patients with PIK3CA activating mutations have included Fibroadipose hyperplasia or Overgrowth (FAO), Hemihyperplasia Multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal (CLOVES) syndrome, macrodactyly, Fibroadipose Infiltrating Lipomatosis, and the related megalencephaly syndromes, Megalencephaly-Capillary Malformation (MCAP or M-CM) and Dysplastic Megalencephaly (DMEG). A workshop was convened at the National Institutes of Health (NIH) to discuss and develop a consensus document regarding diagnosis and treatment of patients with PIK3CA-associated somatic overgrowth disorders. Participants in the workshop included a group of researchers from several institutions who have been studying these disorders and have published their findings, as well as representatives from patient-advocacy and support groups. The umbrella term of “PIK3CA-Related Overgrowth Spectrum (PROS)” was agreed upon to encompass both the known and emerging clinical entities associated with somatic PIK3CA mutations including, macrodactyly, FAO, HHML, CLOVES, and related megalencephaly conditions. Key clinical diagnostic features and criteria for testing were proposed, and testing approaches summarized. Preliminary recommendations for a uniform approach to assessment of overgrowth and molecular diagnostic testing were determined. Future areas to address include the surgical management of overgrowth tissue and vascular anomalies, the optimal approach to thrombosis risk, and the testing of potential pharmacologic therapies.
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影响因子：
30.8
作者：
Lindhurst, Marjorie J.;Parker, Victoria E. R.;Payne, Felicity;Sapp, Julie C.;Rudge, Simon;Harris, Julie;Witkowski, Alison M.;Zhang, Qifeng;Groeneveld, Matthijs P.;Scott, Carol E.;Daly, Allan;Huson, Susan M.;Tosi, Laura L.;Cunningham, Michael L.;Darling, Thomas N.;Geer, Joseph;Gucev, Zoran;Sutton, V. Reid;Tziotzios, Christos;Dixon, Adrian K.;Helliwell, Timothy;O'Rahilly, Stephen;Savage, David B.;Wakelam, Michael J. O.;Barroso, Ines;Biesecker, Leslie G.;Semple, Robert K.
通讯作者：
Semple, Robert K.
影响因子：
2
作者：
Keppler-Noreuil, Kim M.;Sapp, Julie C.;Lindhurst, Marjorie J.;Parker, Victoria E. R.;Blumhorst, Cathy;Darling, Thomas;Tosi, Laura L.;Huson, Susan M.;Whitehouse, Richard W.;Jakkula, Eveliina;Grant, Ian;Balasubramanian, Meena;Chandler, Kate E.;Fraser, Jamie L.;Gucev, Zoran;Crow, Yanick J.;Brennan, Leslie Manace;Clark, Robin;Sellars, Elizabeth A.;Pena, Loren D. M.;Krishnamurty, Vidya;Shuen, Andrew;Braverman, Nancy;Cunningham, Michael L.;Sutton, V. Reid;Tasic, Velibor;Graham, John M., Jr.;Geer, Joseph, Jr.;Henderson, Alex;Semple, Robert K.;Biesecker, Leslie G.
通讯作者：
Biesecker, Leslie G.
DOI：
10.1073/pnas.0701005104
发表时间：
2007-03-27
影响因子：
11.1
作者：
Gymnopoulos, Marco;Elsliger, Marc-Andre;Vogt, Peter K.
通讯作者：
Vogt, Peter K.
影响因子：
9.8
作者：
Kurek, Kyle C.;Luks, Valerie L.;Warman, Matthew L.
通讯作者：
Warman, Matthew L.
DOI：
10.1126/science.1210878
发表时间：
2011-10-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hussain K;Challis B;Rocha N;Payne F;Minic M;Thompson A;Daly A;Scott C;Harris J;Smillie BJ;Savage DB;Ramaswami U;De Lonlay P;O'Rahilly S;Barroso I;Semple RK
通讯作者：
Semple RK