scholarly journals Assessing the Gene-Disease Association of 19 Genes with the RASopathies using the ClinGen Gene Curation Framework

2018 ◽  
Author(s):  
Andrew Grant ◽  
Brandon Cushman ◽  
Hélène Cavé ◽  
Mitchell W. Dillon ◽  
Bruce D. Gelb ◽  
...  
Keyword(s):  
Noonan Syndrome ◽  
Expert Panel ◽  
Disease Association ◽  
Costello Syndrome ◽  
Ministry Of Education ◽  
Genome Research ◽  
National Human ◽  
Anagen Hair ◽  
Multiple Lentigines ◽  
Literature Curation

AbstractThe RASopathies are a complex group of diseases regarding phenotype and genetic etiology. The ClinGen RASopathy Expert Panel assessed published and other publicly available evidence supporting the association of 19 genes with RASopathy conditions. Using the semi-quantitative literature curation method developed by the ClinGen Gene Curation Working Group, evidence for each gene was curated and scored for Noonan syndrome, Costello syndrome, cardiofaciocutaneous (CFC) syndrome, Noonan syndrome with multiple lentigines (NSML), and Noonan-like syndrome with loose anagen hair (NS/LAH).The curated evidence supporting each gene-disease relationship was then discussed and approved by the ClinGen RASopathy Expert Panel. Each association’s strength was classified as Definitive, Strong, Moderate, Limited, Disputed, or No Evidence. Eleven genes were classified as definitively associated with at least one RASopathy condition. Two genes classified as strong for association with at least one RASopathy condition while one gene was moderate and three were limited. The RAS EP also refuted the association of two genes for a RASopathy condition. Overall, our results provide a greater understanding of the different gene-disease relationships within the RASopathies and can help guide and direct clinicians, patients and researchers who are identifying variants in individuals with a suspected RASopathyGRANT NUMBERS:Research reported in this publication was supported by the National Human Genome Research Institute (NHGRI) under award number U41HG006834. MZ received support from German Federal Ministry of Education and Research (BMBF): NSEuroNet (FKZ 01GM1602A), GeNeRARe (FKZ 01GM1519A).

RASopathies in multidisciplinary pediatric hospita

2020 ◽  
pp. 21-23
Author(s):  
Н.В. Журкова ◽  
Л.А. Гандаева ◽  
А.А. Пушков ◽  
Е.Н. Басаргина ◽  
А.В. Пахомов ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Noonan Syndrome ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Costello Syndrome ◽  
Inherited Diseases ◽  
Cardiofaciocutaneous Syndrome ◽  
Genes Encoding ◽  
Mitogen Activated Protein ◽  
Anagen Hair

RAS-патии - группа наследственных заболеваний, возникающая вследствие нарушения регуляции функции RAS/MAPK внутриклеточных путей (Ras/mitogen-activated protein kinase). Суммарная частота заболеваний данной группы - 1 случай на 1000 новорожденных. Наиболее часто среди RAS-патий встречается синдром Нунан. В настоящее время описано 13 генов, мутации которых отвечают за развитие данного заболевания, включая ген SHOC2, ассоциированный с Нунан-подобным синдромом и измененной структурой волос (Noonan-like syndrome with loose anagen hair) и ген LZTR1, мутации в котором приводят к развитию синдрома Нунан, тип 2 с аутосомно-рецессивным типом наследования. RASopathies - group of inherited diseases, caused by mutations in genes, encoding components or regulators of the Ras/mitogen-activated protein kinase (MAPK) pathway. We identified 28 patients with inherited diseases from RASopathies: 61% - with Noonan syndrome, 14 % - with Cardiofaciocutaneous syndrome, 14% - with Costello syndrome - 11% - Noonan syndrome-like with loose anagen hair. Mutation c.770C>T, p.S257L in RAF1gene is most common in hypertrophic cardiomyopathy patients with Noonan syndrome. All patients with Noonan syndrome-like with loose anagen hair have mutation c.4A>G , p.S2G in SHOC2 gene.

scholarly journals The RASopathy Family: Consequences of Germline Activation of the RAS/MAPK Pathway

2018 ◽  
Vol 39 (5) ◽  
pp. 676-700 ◽  
Author(s):  
Mylène Tajan ◽  
Romain Paccoud ◽  
Sophie Branka ◽  
Thomas Edouard ◽  
Armelle Yart
Keyword(s):  
Noonan Syndrome ◽  
Mapk Pathway ◽  
Genetic Disorders ◽  
Mapk Signaling ◽  
Mendelian Inheritance ◽  
Disease Genes ◽  
Type I ◽  
Future Directions ◽  
Legius Syndrome ◽  
Anagen Hair

Abstract Noonan syndrome [NS; Mendelian Inheritance in Men (MIM) #163950] and related syndromes [Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome; MIM #151100), Noonan-like syndrome with loose anagen hair (MIM #607721), Costello syndrome (MIM #218040), cardio-facio-cutaneous syndrome (MIM #115150), type I neurofibromatosis (MIM #162200), and Legius syndrome (MIM #611431)] are a group of related genetic disorders associated with distinctive facial features, cardiopathies, growth and skeletal abnormalities, developmental delay/mental retardation, and tumor predisposition. NS was clinically described more than 50 years ago, and disease genes have been identified throughout the last 3 decades, providing a molecular basis to better understand their physiopathology and identify targets for therapeutic strategies. Most of these genes encode proteins belonging to or regulating the so-called RAS/MAPK signaling pathway, so these syndromes have been gathered under the name RASopathies. In this review, we provide a clinical overview of RASopathies and an update on their genetics. We then focus on the functional and pathophysiological effects of RASopathy-causing mutations and discuss therapeutic perspectives and future directions.

scholarly journals Noonan syndrome with multiple lentigines and associated craniosynostosis

2018 ◽  
Vol 43 (3) ◽  
pp. 357-359 ◽  
Author(s):  
B. S. McDonald ◽  
M. Pigors ◽  
D. P. Kelsell ◽  
E. A. O'Toole ◽  
E. Burkitt-Wright ◽  
...  
Keyword(s):  
Noonan Syndrome ◽  
Multiple Lentigines

Widespread keratosis pilaris in a patient with Noonan syndrome with multiple lentigines

2018 ◽  
Vol 57 (11) ◽  
pp. e140-e141
Author(s):  
Seda Purnak ◽  
Vehap Topçu ◽  
Büşranur Çavdarlı ◽  
Elçin Kadan ◽  
Başak Yalçın
Keyword(s):  
Noonan Syndrome ◽  
Multiple Lentigines
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