Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation
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Dosyalar
Tarih
2016
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Nature Publishing Group
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
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. © 2016 American College of Medical Genetics and Genomics.
Açıklama
Anahtar Kelimeler
hypertrophic cardiomyopathy, Noonan syndrome, oncogenic mutations, RAS-MAPK signaling pathway, RASopathies, adolescent, adult, Article, child, clinical article, clinical feature, codon, female, gene, gene mutation, genetic association, genetic variability, genotype phenotype correlation, germline mutation, human, hypertrophic cardiomyopathy, infant, lymphatic system disease, male, middle aged, missense mutation, Noonan syndrome, preschool child, RIT1 gene, school child, congenital heart malformation, genetic association study, genetics, genotype, Noonan syndrome, pathology, pedigree, phenotype, Ras protein, RIT1 protein, human, Cardiomyopathy, Hypertrophic, Female, Genetic Association Studies, Genotype, Germ-Line Mutation, Heart Defects, Congenital, Humans, Male, Noonan Syndrome, Pedigree, Phenotype, ras Proteins
Kaynak
Genetics in Medicine
WoS Q Değeri
Scopus Q Değeri
Q1
Cilt
18
Sayı
12
