排序方式: 共有61条查询结果,搜索用时 31 毫秒
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Karen W. Gripp Lindsey A. Morse Marni Axelrad Kathryn C. Chatfield Aaron Chidekel William Dobyns Daniel Doyle Bronwyn Kerr Angela E. Lin David D. Schwartz Barbara J. Sibbles Dawn Siegel Suma P. Shankar David A. Stevenson Mihir M. Thacker K. Nicole Weaver Sue M. White Katherine A. Rauen 《American journal of medical genetics. Part A》2019,179(9):1725-1744
Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence‐based guidelines due to the lack of data for this rare condition. 相似文献
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Chao‐Kai Hsu Ryo Saito Arti Nanda Ellie Rashidghamat Hejab Al‐Ajmi Julia Yu‐Yun Lee Michihiro Hide John A McGrath 《The Australasian journal of dermatology》2017,58(1):58-60
Naevus sebaceus has recently been shown to result from post‐zygotic mutations in HRAS, KRAS or occasionally NRAS. We present details of a neonate with extensive naevus sebaceus in whom we identified a pathogenic mutation in HRAS (c.37G > C; p.Gly13Arg), but only in lesional skin DNA, consistent with a mosaic RASopathy. This case highlights the clinicopathological and molecular findings of this naevoid disorder as well as the key issues in the clinical assessment and management of such patients. 相似文献
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Recent developments in neurofibromatoses and RASopathies: Management,diagnosis and current and future therapeutic avenues 下载免费PDF全文
Katherine A. Rauen Susan M. Huson Emma Burkitt‐Wright D. Gareth Evans Said Farschtschi Rosalie E. Ferner David H. Gutmann C. Oliver Hanemann Bronwyn Kerr Eric Legius Luis F. Parada Michael Patton Juha Peltonen Nancy Ratner Vincent M. Riccardi Thijs van der Vaart Miikka Vikkula David H. Viskochil Martin Zenker Meena Upadhyaya 《American journal of medical genetics. Part A》2015,167(1):1-10
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MAP2K2 mutation as a cause of cardio‐facio‐cutaneous syndrome in an infant with a severe and fatal course of the disease 下载免费PDF全文
Monika Gos Robert Smigiel Teresa Kaczan Aleksandra Landowska Anna Abramowicz Malgorzata Sasiadek Jerzy Bal 《American journal of medical genetics. Part A》2018,176(7):1670-1674
Cardio‐facio‐cutaneous syndrome (CFCS), a rare congenital disorder of RASopathies, displays high phenotypic variability. Complications during pregnancy and in the perinatal period are commonly reported. Polyhydramnios is observed in over half of pregnancies and might occur with fetal macrocephaly, macrosomia, and/or heart defects. Premature birth is not uncommon and any complications like respiratory insufficiency, edema, and feeding difficulties are present and might delay accurate clinical diagnosis. Besides neonatal complications, CFCS newborns and later infants have distinctive dysmorphic features usually accompanied by neurological (hypotonia with motor delay, neurocognitive delay) findings. Also, heart defects usually present at birth. Herein, we present the case of a female baby born prematurely from a pregnancy complicated with polyhydramnios, presenting at birth with craniofacial features typical for RASopathies, heart defects, neurological abnormalities, and hyperkeratosis unusual for a neonatal period. Due to the presence of a heart defect and other complications related to premature birth, the course of the disease was severe with a fatal outcome at the age of 9 months. The RASopathy, particularly CFCS, clinical diagnosis was confirmed and de novo p.Phe57Ile mutation in MAP2K2 was identified. 相似文献
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C P Kratz L Franke H Peters N Kohlschmidt B Kazmierczak U Finckh A Bier B Eichhorn C Blank C Kraus J Kohlhase S Pauli G Wildhardt K Kutsche B Auber A Christmann N Bachmann D Mitter F W Cremer K Mayer C Daumer-Haas C Nevinny-Stickel-Hinzpeter F Oeffner G Schlüter M Gencik B überlacker C Lissewski I Schanze M H Greene C Spix M Zenker 《British journal of cancer》2015,112(8):1392-1397
Background:
Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These ‘RASopathies'' also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown.Methods:
We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a group of 735 individuals with germline mutations in Ras signalling pathway genes by matching their information with the German Childhood Cancer Registry.Results:
We observed 12 cases of cancer in the entire RASopathy cohort vs 1.12 expected (based on German population-based incidence rates). This corresponds to a 10.5-fold increased risk of all childhood cancers combined (standardised incidence ratio (SIR)=10.5, 95% confidence interval=5.4–18.3). The specific cancers included juvenile myelomonocytic leukaemia=4; brain tumour=3; acute lymphoblastic leukaemia=2; rhabdomyosarcoma=2; and neuroblastoma=1. The childhood cancer SIR in Noonan syndrome patients was 8.1, whereas that for Costello syndrome patients was 42.4.Conclusions:
These data comprise the first quantitative evidence documenting that the germline mutations in Ras signalling pathway genes are associated with increased risks of both childhood leukaemia and solid tumours. 相似文献9.
Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis 下载免费PDF全文
S. Boppudi N. Bögershausen H.B. Hove E.F. Percin D. Aslan R. Dvorsky G. Kayhan Y. Li C. Cursiefen I. Tantcheva‐Poor P.B. Toft O. Bartsch C. Lissewski I. Wieland S. Jakubiczka B. Wollnik M.R. Ahmadian M. Zenker 《Clinical genetics》2016,90(4):334-342
Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor‐like lesions, and others. About 20 cases with OES and more than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole‐genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report the results of molecular genetic studies in three patients with OES and one with ECCL. In all four cases, Sanger sequencing of the KRAS gene in DNA from lesional tissue detected mutations affecting codon 146 (p.Ala146Val, p.Ala146Thr) at variable levels of mosaicism. Our findings thus corroborate the evidence of OES being a mosaic RASopathy and confirm the common etiology of OES and ECCL. KRAS codon 146 mutations, as well as the previously reported OES‐associated alterations, are known oncogenic KRAS mutations with distinct functional consequences. Considering the phenotype and genotype spectrum of mosaic RASopathies, these findings suggest that the wide phenotypic variability does not only depend on the tissue distribution but also on the specific genotype. 相似文献