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Neurofibromatosis–Noonan syndrome: Molecular evidence of the concurrence of both disorders in a patient
Author(s) -
Bertola Debora R.,
Pereira Alexandre C.,
Passetti Fábio,
de Oliveira Paulo S.L.,
Messiaen Ludwine,
Gelb Bruce D.,
Kim Chong A.,
Krieger José Eduardo
Publication year - 2005
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.30813
Subject(s) - noonan syndrome , ptpn11 , neurofibromatosis , costello syndrome , neurofibromin 1 , transversion , short stature , genetics , biology , signal transduction , mutation , cancer research , medicine , endocrinology , kras , gene
Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial anomalies, webbed neck, sternal deformity, heart defects, and, in males, cryptorchidism. PTPN11 encodes SHP2, an important component of several signal transduction pathways that acts as a positive regulator of RAS‐mitogen activated protein kinase signaling. Neurofibromatosis type 1 (NF1) is another autosomal dominant disorder characterized by hamartomas in multiple organs. The NF1 gene encodes a GAP‐related protein, which acts as a negative regulator of the Ras‐mediated signal transduction pathway. Clinical overlap between both syndromes, neurofibromatosis–Noonan syndrome (NFNS) is well known. We studied a female patient with typical findings of NFNS and found two mutations: a novel PTPN11 transversion, 1909A → G, resulting in Gln510Arg, and an NF1 transversion, 2531A → G, resulting in Leu844Arg. She inherited the PTPN11 mutation from her father and had a de novo NF1 mutation. This is the first report of molecular concurrence of both disorders in the same patient. © 2005 Wiley‐Liss, Inc.