Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation
Standard
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, Jahrgang 18, Nr. 12, 04.2016, S. 1226-1234.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
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 -