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Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation

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Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation. / Kouz, Karim; Lissewski, Christina; Spranger, Stephanie; Mitter, Diana; Riess, Angelika; Lopez-Gonzalez, Vanesa; Lüttgen, Sabine; Aydin, Hatip; von Deimling, Florian; Evers, Christina; Hahn, Andreas; Hempel, Maja; Issa, Ulrike; Kahlert, Anne-Karin; Lieb, Adrian; Villavicencio-Lorini, Pablo; Ballesta-Martinez, Maria Juliana; Nampoothiri, Sheela; Ovens-Raeder, Angela; Puchmajerová, Alena; Satanovskij, Robin; Seidel, Heide; Unkelbach, Stephan; Zabel, Bernhard; Kutsche, Kerstin; Zenker, Martin.

In: GENET MED, Vol. 18, No. 12, 04.2016, p. 1226-1234.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kouz, K, Lissewski, C, Spranger, S, Mitter, D, Riess, A, Lopez-Gonzalez, V, Lüttgen, S, Aydin, H, von Deimling, F, Evers, C, Hahn, A, Hempel, M, Issa, U, Kahlert, A-K, Lieb, A, Villavicencio-Lorini, P, Ballesta-Martinez, MJ, Nampoothiri, S, Ovens-Raeder, A, Puchmajerová, A, Satanovskij, R, Seidel, H, Unkelbach, S, Zabel, B, Kutsche, K & Zenker, M 2016, 'Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation', GENET MED, vol. 18, no. 12, pp. 1226-1234. https://doi.org/10.1038/gim.2016.32

APA

Kouz, K., Lissewski, C., Spranger, S., Mitter, D., Riess, A., Lopez-Gonzalez, V., Lüttgen, S., Aydin, H., von Deimling, F., Evers, C., Hahn, A., Hempel, M., Issa, U., Kahlert, A-K., Lieb, A., Villavicencio-Lorini, P., Ballesta-Martinez, M. J., Nampoothiri, S., Ovens-Raeder, A., ... Zenker, M. (2016). Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation. GENET MED, 18(12), 1226-1234. https://doi.org/10.1038/gim.2016.32

Vancouver

Kouz K, Lissewski C, Spranger S, Mitter D, Riess A, Lopez-Gonzalez V et al. Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation. GENET MED. 2016 Apr;18(12):1226-1234. https://doi.org/10.1038/gim.2016.32

Bibtex

@article{eed1b010ea1e4a389f6ff6fb95eccb8e,
title = "Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation",
abstract = "PURPOSE: Noonan syndrome (NS) is an autosomal-dominant disorder characterized by craniofacial dysmorphism, growth retardation, cardiac abnormalities, and learning difficulties. It belongs to the RASopathies, which are caused by germ-line mutations in genes encoding components of the RAS mitogen-activated protein kinase (MAPK) pathway. RIT1 was recently reported as a disease gene for NS, but the number of published cases is still limited.METHODS: We sequenced RIT1 in 310 mutation-negative individuals with a suspected RASopathy and prospectively in individuals who underwent genetic testing for NS. Using a standardized form, we recorded clinical features of all RIT1 mutation-positive patients. Clinical and genotype data from 36 individuals with RIT1 mutation reported previously were reviewed.RESULTS: Eleven different RIT1 missense mutations, three of which were novel, were identified in 33 subjects from 28 families; codons 57, 82, and 95 represent mutation hotspots. In relation to NS of other genetic etiologies, prenatal abnormalities, cardiovascular disease, and lymphatic abnormalities were common in individuals with RIT1 mutation, whereas short stature, intellectual problems, pectus anomalies, and ectodermal findings were less frequent.CONCLUSION: RIT1 is one of the major genes for NS. The RIT1-associated phenotype differs gradually from other NS subtypes, with a high prevalence of cardiovascular manifestations, especially hypertrophic cardiomyopathy, and lymphatic problems.Genet Med advance online publication 21 April 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.32.",
author = "Karim Kouz and Christina Lissewski and Stephanie Spranger and Diana Mitter and Angelika Riess and Vanesa Lopez-Gonzalez and Sabine L{\"u}ttgen and Hatip Aydin and {von Deimling}, Florian and Christina Evers and Andreas Hahn and Maja Hempel and Ulrike Issa and Anne-Karin Kahlert and Adrian Lieb and Pablo Villavicencio-Lorini and Ballesta-Martinez, {Maria Juliana} and Sheela Nampoothiri and Angela Ovens-Raeder and Alena Puchmajerov{\'a} and Robin Satanovskij and Heide Seidel and Stephan Unkelbach and Bernhard Zabel and Kerstin Kutsche and Martin Zenker",
year = "2016",
month = apr,
doi = "10.1038/gim.2016.32",
language = "English",
volume = "18",
pages = "1226--1234",
journal = "GENET MED",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

RIS

TY - JOUR

T1 - Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation

AU - Kouz, Karim

AU - Lissewski, Christina

AU - Spranger, Stephanie

AU - Mitter, Diana

AU - Riess, Angelika

AU - Lopez-Gonzalez, Vanesa

AU - Lüttgen, Sabine

AU - Aydin, Hatip

AU - von Deimling, Florian

AU - Evers, Christina

AU - Hahn, Andreas

AU - Hempel, Maja

AU - Issa, Ulrike

AU - Kahlert, Anne-Karin

AU - Lieb, Adrian

AU - Villavicencio-Lorini, Pablo

AU - Ballesta-Martinez, Maria Juliana

AU - Nampoothiri, Sheela

AU - Ovens-Raeder, Angela

AU - Puchmajerová, Alena

AU - Satanovskij, Robin

AU - Seidel, Heide

AU - Unkelbach, Stephan

AU - Zabel, Bernhard

AU - Kutsche, Kerstin

AU - Zenker, Martin

PY - 2016/4

Y1 - 2016/4

N2 - PURPOSE: Noonan syndrome (NS) is an autosomal-dominant disorder characterized by craniofacial dysmorphism, growth retardation, cardiac abnormalities, and learning difficulties. It belongs to the RASopathies, which are caused by germ-line mutations in genes encoding components of the RAS mitogen-activated protein kinase (MAPK) pathway. RIT1 was recently reported as a disease gene for NS, but the number of published cases is still limited.METHODS: We sequenced RIT1 in 310 mutation-negative individuals with a suspected RASopathy and prospectively in individuals who underwent genetic testing for NS. Using a standardized form, we recorded clinical features of all RIT1 mutation-positive patients. Clinical and genotype data from 36 individuals with RIT1 mutation reported previously were reviewed.RESULTS: Eleven different RIT1 missense mutations, three of which were novel, were identified in 33 subjects from 28 families; codons 57, 82, and 95 represent mutation hotspots. In relation to NS of other genetic etiologies, prenatal abnormalities, cardiovascular disease, and lymphatic abnormalities were common in individuals with RIT1 mutation, whereas short stature, intellectual problems, pectus anomalies, and ectodermal findings were less frequent.CONCLUSION: RIT1 is one of the major genes for NS. The RIT1-associated phenotype differs gradually from other NS subtypes, with a high prevalence of cardiovascular manifestations, especially hypertrophic cardiomyopathy, and lymphatic problems.Genet Med advance online publication 21 April 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.32.

AB - PURPOSE: Noonan syndrome (NS) is an autosomal-dominant disorder characterized by craniofacial dysmorphism, growth retardation, cardiac abnormalities, and learning difficulties. It belongs to the RASopathies, which are caused by germ-line mutations in genes encoding components of the RAS mitogen-activated protein kinase (MAPK) pathway. RIT1 was recently reported as a disease gene for NS, but the number of published cases is still limited.METHODS: We sequenced RIT1 in 310 mutation-negative individuals with a suspected RASopathy and prospectively in individuals who underwent genetic testing for NS. Using a standardized form, we recorded clinical features of all RIT1 mutation-positive patients. Clinical and genotype data from 36 individuals with RIT1 mutation reported previously were reviewed.RESULTS: Eleven different RIT1 missense mutations, three of which were novel, were identified in 33 subjects from 28 families; codons 57, 82, and 95 represent mutation hotspots. In relation to NS of other genetic etiologies, prenatal abnormalities, cardiovascular disease, and lymphatic abnormalities were common in individuals with RIT1 mutation, whereas short stature, intellectual problems, pectus anomalies, and ectodermal findings were less frequent.CONCLUSION: RIT1 is one of the major genes for NS. The RIT1-associated phenotype differs gradually from other NS subtypes, with a high prevalence of cardiovascular manifestations, especially hypertrophic cardiomyopathy, and lymphatic problems.Genet Med advance online publication 21 April 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.32.

U2 - 10.1038/gim.2016.32

DO - 10.1038/gim.2016.32

M3 - SCORING: Journal article

C2 - 27101134

VL - 18

SP - 1226

EP - 1234

JO - GENET MED

JF - GENET MED

SN - 1098-3600

IS - 12

ER -