Document Detail


A variable combination of features of Noonan syndrome and neurofibromatosis type I are caused by mutations in the NF1 gene.
MedLine Citation:
PMID:  17103458     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Signs of neurofibromatosis type 1 (NF1) and Noonan syndrome (NS), two distinct autosomal dominant disorders, occur together in patients reported as Watson syndrome (WS), neurofibromatosis-Noonan syndrome (NFNS), partial LEOPARD syndrome, NS with features of NF1, and NF1 with Noonan-like features. The molecular basis of these combined phenotypes was poorly understood and controversially discussed over several decades. Only recently, there is increasing evidence for WS and NFNS being allelic to NF1 in the majority of patients. In this study we describe seven novel patients from five unrelated families with variable phenotypes of the NF1-NS spectrum which were systematically analyzed for mutations in the disease-causing genes NF1 for NF1 and PTPN11 for NS. Heterozygous mutations or deletions of NF1 were identified in all patients, while no PTPN11 mutation was found. The NF1 mutation segregated with the phenotype in both familial cases. These results support the hypothesis that variable phenotypes of the NF1-NS spectrum represent variants of NF1 in the majority of cases. Constitutive deregulation of the Ras pathway either through activating mutations of PTPN11 or through haploinsufficiency of neurofibromin, which acts as a Ras-inactivating GTP-ase, is probably the common pathogenetic mechanism explaining the phenotypic overlap of NS and NF1.
Authors:
Ulrike Hüffmeier; Martin Zenker; Juliane Hoyer; Raimund Fahsold; Anita Rauch
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Publication Detail:
Type:  Case Reports; Journal Article    
Journal Detail:
Title:  American journal of medical genetics. Part A     Volume:  140     ISSN:  1552-4825     ISO Abbreviation:  Am. J. Med. Genet. A     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-27     Completed Date:  2007-01-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101235741     Medline TA:  Am J Med Genet A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2749-56     Citation Subset:  IM    
Copyright Information:
(c) 2006 Wiley-Liss, Inc.
Affiliation:
Institute of Human Genetics, University Erlangen-Nuremberg, Erlangen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adult
Base Sequence
Child
Child, Preschool
DNA / genetics
DNA Mutational Analysis
Female
Genes, Neurofibromatosis 1*
Humans
Infant
Infant, Newborn
Male
Mutation*
Neurofibromatosis 1 / complications*,  genetics*
Noonan Syndrome / complications*,  genetics*
Phenotype
Chemical
Reg. No./Substance:
9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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