Prenatal findings in cardio‐facio‐cutaneous syndrome
Our study was designed to analyze prenatal manifestations in patients affected with cardio‐facio‐cutaneous syndrome (CFCS), in order to define indications of DNA testing in utero. Prenatal features were extracted from a national database and additional data were collected from 16 families contacted through the French association of CFC‐Costello syndrome. We collected results of ultrasound scan (USS) biometrics, presence of congenital birth defects, and polyhydramnios. From the database, increased nuchal translucency was present in 13% of pregnancies, polyhydramnios in 52%, macrosomia and/or macrocephaly in 16%. Of th...
Source: American Journal of Medical Genetics Part A - October 23, 2015 Category: Genetics & Stem Cells Authors: Ludivine Templin, Clarisse Baumann, Tiffany Busa, Hélène Heckenroth, Nathalie Pouvreau, Annick Toutain, Hélène Cave, Alain Verloes, Sabine Sigaudy, Nicole Philip Tags: Research Article Source Type: research
13q31.1 microdeletion: a prenatal case report with macrocephaly and macroglossia.
We report on a female fetus with macrocephaly and macroglossia harbouring 13q31.1 microdeletion encompassing three genes: SPRY2, NDFIP2 and RBM26. NDFIP2 protein is involved in ubiquitination and in Ras/mitogen-activated protein kinase (MAPK) signaling pathways. SPRY2 protein is part of Sprout protein family and inhibits the Ras/MAPK pathways. Ras/MAPK pathway plays important role in complex cellular programs including cell differentiation and proliferation. Germline mutations in genes encoding protein involved in the MAPK cascade is responsible for a wide family of developmental disorders known as RASopathies. Some RASopa...
Source: European Journal of Medical Genetics - September 10, 2015 Category: Genetics & Stem Cells Authors: Poreau B, Lin S, Bosson C, Dieterich K, Satre V, Devillard F, Guigue V, Ronin C, Brouillet S, Barbier C, Jouk PS, Coutton C Tags: Eur J Med Genet Source Type: research
Differential effects of HRAS mutation on LTP-like activity induced by different protocols of repetitive transcranial magnetic stimulation
Conclusions CS patients are characterized by an impairment of iTBS-related LTP-like phenomena besides enhanced PAS-induced after-effects, suggesting that HRAS-dependent signalling pathways have a differential influence on PAS- and iTBS-induced plasticity in humans. (Source: Brain Stimulation)
Source: Brain Stimulation - September 3, 2015 Category: Neurology Source Type: research
Differential effects of HRAS mutation on LTP-like activity induced by different protocols of repetitive transcranial magnetic stimulation
• Costello syndrome (CS) is due to a gain of function mutation in HRAS that is involved in LTP-like phenomena• PAS and iTBS induce a similar enhancement in brain excitability in healthy subjects.• PAS induces an extremely pronounced increase in motor cortex excitability in CS but till now no data about the effects of iTBS are available in these patients.• Unlike healthy subjects, PAS and iTBS induced differential effects on motor cortex excitability in CS.• HRAS differentially influences iTBS- and PAS-induced plasticity in humans. (Source: BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation)
Source: BRAIN STIMULATION: Basic, Translational, and Clinical Research in Neuromodulation - September 2, 2015 Category: Neurology Authors: Michele Dileone, Federico Ranieri, Lucia Florio, Fioravante Capone, Gabriella Musumeci, Chiara Leoni, Laura Mordillo-Mateos, Marco Tartaglia, Giuseppe Zampino, Vincenzo Di Lazzaro Source Type: research
The role of p19 and p21 H-Ras proteins and mutants in miRNA expression in cancer and a Costello syndrome cell model
Conclusions:
These results allow us to conclude that the H-Ras G12S mutation plays an important role in miRNA expression and open up a new line of study to understand the consequences of this mutation on Costello syndrome. Furthermore, they suggest that oncogenes may have a sufficiently important impact on miRNA expression to promote the development of numerous cancers. (Source: BMC Medical Genetics)
Source: BMC Medical Genetics - July 3, 2015 Category: Genetics & Stem Cells Authors: Roseli García-CruzMaria CamatsGeorge CalinChang-Gong LiuStefano VoliniaCristian TaccioliCarlo CroceMontse Bach-Elias Source Type: research
[Perspective] “RASopathic” astrocytes constrain neural plasticity
Over the past decade, mutations in genes encoding RAS family members, other components of an intracellular signaling cascade that RAS controls, and proteins that modify the cascade have been recognized as causes of developmental syndromes. Collectively, these syndromes are often referred to as “RASopathies.” Not surprisingly, RASopathies have numerous manifestations, including propensity to cancer, craniofacial abnormalities, cardiac defects, cutaneous abnormalities, neurodevelopmental delay, and varying degrees of cognitive dysfunction. Uncovering the causes and developing treatments for the neurodevelopmental abnorma...
Source: Science: Current Issue - May 8, 2015 Category: Science Authors: Lei Xing Tags: Neurodevelopment Source Type: research
[Research Articles] Dysregulation of astrocyte extracellular signaling in Costello syndrome
Astrocytes produce an assortment of signals that promote neuronal maturation according to a precise developmental timeline. Is this orchestrated timing and signaling altered in human neurodevelopmental disorders? To address this question, the astroglial lineage was investigated in two model systems of a developmental disorder with intellectual disability caused by mutant Harvey rat sarcoma viral oncogene homolog (HRAS) termed Costello syndrome: mutant HRAS human induced pluripotent stem cells (iPSCs) and transgenic mice. Human iPSCs derived from patients with Costello syndrome differentiated to astroglia more rapidly in vi...
Source: Science Translational Medicine - May 6, 2015 Category: Biomedical Science Authors: Krencik, R., Hokanson, K. C., Narayan, A. R., Dvornik, J., Rooney, G. E., Rauen, K. A., Weiss, L. A., Rowitch, D. H., Ullian, E. M. Tags: Research Articles Source Type: research
Uniparental Trisomy of a Mutated HRAS Proto-Oncogene in Embryonal Rhabdomyosarcoma of a Patient With Costello Syndrome [DIAGNOSIS IN ONCOLOGY]
(Source: Journal of Clinical Oncology)
Source: Journal of Clinical Oncology - April 29, 2015 Category: Cancer & Oncology Authors: Menke, Pauli, Sigler, Kuhnle, Shoukier, Zoll, Ganster, Salinas-Riester, Schaefer Tags: Rhabdomyosarcoma & Soft Tissue Sarcoma, Diagnosis & Staging, Rhabdo & Other Soft Tissue Sarcomas:, MRI DIAGNOSIS IN ONCOLOGY Source Type: research
An attenuated phenotype of Costello syndrome in three unrelated individuals with a HRAS c.179G>A (p.Gly60Asp) mutation correlates with uncommon functional consequences
Heterozygous germline mutations in the proto‐oncogene HRAS cause Costello syndrome (CS), an intellectual disability condition with severe failure to thrive, cardiac abnormalities, predisposition to tumors, and neurologic abnormalities. More than 80% of patients share the HRAS mutation c.34G>A (p.Gly12Ser) associated with the typical, relatively homogeneous phenotype. Rarer mutations occurred in individuals with an attenuated phenotype and less characteristic facial features. Most pathogenic HRAS alterations affect hydrolytic HRAS activity resulting in constitutive activation. “Gain‐of‐function” and “hyperact...
Source: American Journal of Medical Genetics Part A - April 25, 2015 Category: Genetics & Stem Cells Authors: Karen W. Gripp, Katia Sol‐Church, Patroula Smpokou, Gail E. Graham, David A. Stevenson, Heather Hanson, David H. Viskochil, Laura C. Baker, Bridget Russo, Nick Gardner, Deborah L. Stabley, Verena Kolbe, Georg Rosenberger Tags: Research Article Source Type: research
The third international meeting on genetic disorders in the RAS/MAPK pathway: Towards a therapeutic approach
“The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach” was held at the Renaissance Orlando at SeaWorld Hotel (August 2–4, 2013). Seventy‐one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions...
Source: American Journal of Medical Genetics Part A - April 21, 2015 Category: Genetics & Stem Cells Authors: Bruce Korf, Reza Ahmadian, Judith Allanson, Yoko Aoki, Annette Bakker, Emma Burkitt Wright, Brian Denger, Ype Elgersma, Bruce D. Gelb, Karen W. Gripp, Bronwyn Kerr, Maria Kontaridis, Conxi Lazaro, Corinne Linardic, Reymundo Lozano, Calum A. MacRae, Ludwin Tags: Research Article Source Type: research
Rhabdomyosarcomas in children with neurofibromatosis type I: A national historical cohort
ConclusionsPatients with neurofibromatosis are prone to develop embryonal‐type RMS that require the same treatment as sporadic cases. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)
Source: Pediatric Blood and Cancer - April 20, 2015 Category: Cancer & Oncology Authors: Anne Crucis, Wilfrid Richer, Laurence Brugières, Christophe Bergeron, Aude Marie‐Cardine, Jean‐Louis Stephan, Pauline Girard, Nadege Corradini, Martine Munzer, Brigitte Lacour, Veronique Minard‐Colin, Sabine Sarnacki, Dominique Ranchere‐Vince, Da Tags: Research Article Source Type: research
PTPN11 mutation manifesting as LEOPARD syndrome associated with hypertrophic plexi and neuropathic pain
Conclusion:
LS caused by PTPN11 mutations may be associated with hypertrophic roots and plexi. Consequently, clinicians should be aware of the possible development of neuropathic pain and consider specific diagnostic work-up and management. (Source: BMC Neurology)
Source: BMC Neurology - April 16, 2015 Category: Neurology Authors: Marianna SpatolaChristian WiderThierry KuntzerAlexandre Croquelois Source Type: research
A germline MTOR mutation in Aboriginal Australian siblings with intellectual disability, dysmorphism, macrocephaly, and small thoraces
We report on three Aboriginal Australian siblings with a unique phenotype which overlaps with known megalencephaly syndromes and RASopathies, including Costello syndrome. A gain‐of‐function mutation in MTOR was identified and represents the first reported human condition due to a germline, familial MTOR mutation. We describe the findings in this family to highlight that (i) the path to determination of pathogenicity was confounded by the lack of genomic reference data for Australian Aboriginals and that (ii) the disease biology, functional analyses in this family, and studies on the tuberous sclerosis complex support c...
Source: American Journal of Medical Genetics Part A - April 6, 2015 Category: Genetics & Stem Cells Authors: Gareth Baynam, Angela Overkov, Mark Davis, Kym Mina, Lyn Schofield, Richard Allcock, Nigel Laing, Matthew Cook, Hugh Dawkins, Jack Goldblatt Tags: Clinical Report Source Type: research
Activated K‐Ras, but not H‐Ras or N‐Ras, regulates brain neural stem cell proliferation in a Raf/Rb‐dependent manner
This article is protected by copyright. All rights reserved. (Source: Stem Cells)
Source: Stem Cells - March 18, 2015 Category: Stem Cells Authors: R. Hugh, F. Bender, Kevin M. Haigis, David H. Gutmann Tags: Tissue‐Specific Stem Cells Source Type: research
Recurrent duplication mutation in HRAS causing mild Costello syndrome in a Chinese patient
We report on a patient with sporadic CS presenting with characteristic craniofacial dysmorphism, congenital cardiopulmonary disorders, intellectual impairment, and skin abnormalities manifesting as loose redundant skin of the hands and feet, acanthosis nigricans, multiple naevi and hypotrichosis. Using Sanger sequencing for the case–parents trio, we detected a de novo insertion mutation (c.187_207dup) in HRAS, which was predicted to result in duplication of amino acids 63–69 (p.E63_D69dup). This mutation was recently described in a mild case of CS, with hyperactivation of HRAS and disrupted capacity to respond to incom...
Source: Clinical And Experimental Dermatology - February 10, 2015 Category: Dermatology Authors: F. Xu, H. J. Wang, Z. M. Lin, B. Yu Tags: Clinical dermatology ● Concise report Source Type: research
