Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/21276
Title: High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype-Phenotype Correlation.
Authors: 
Keywords: 
Mesh: 
Issue Date: Nov-2015
Citation: Hum. Mutat..2015 Nov;(36)11:1052-63
Abstract: Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple café-au-lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan-like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P < 0.0001). Developmental delays and/or learning disabilities were reported in over 50% of patients. Melanocytes cultured from a CALM in a segmental NF1-patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi-exon deletion, providing genetic evidence that p.Arg1809Cys is a loss-of-function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype-phenotype correlation will affect counseling and management of a significant number of patients.
PMID: 26178382
URI: https://hdl.handle.net/20.500.12530/21276
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > FIB H. Infantil U. Niño Jesús > Artículos
Fundaciones e Institutos de Investigación > IIS H. General U. Gregorio Marañón > Artículos
Fundaciones e Institutos de Investigación > IIS H. U. Ramón y Cajal > Artículos

Files in This Item:
File Description SizeFormat 
PMC5049609.pdf226.07 kBAdobe PDFThumbnail
View/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.