Noonan syndrome and neurofibromatosis type I in a family with a novel mutation in NF1
| Autor: | Christina Edeby, Sara Ekvall, Anna-Maja Nyström, Marie-Louise Bondeson, Göran Annerén, Judith Allanson, Gerd Holmström, Malin Elinder |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Neurofibromatosis 1 Neurofibromatosis Noonan syndrome DNA Mutational Analysis Molecular Sequence Data Mutation Missense Protein Structure Secondary Open Reading Frames Internal medicine Genetics medicine Missense mutation Humans Family Neurofibromatosis neoplasms Genetics (clinical) Neurofibromatosis type I Family Characteristics Neurofibromin 1 Base Sequence business.industry Noonan Syndrome p120 GTPase Activating Protein Middle Aged medicine.disease Osteochondrodysplasia nervous system diseases Pedigree PTPN11 Endocrinology Mutation Noonan syndrome Medical genetics Female business |
| Zdroj: | Clinical genetics. 76(6) |
| ISSN: | 1399-0004 |
| Popis: | Noonan syndrome (NS) and neurofibromatosis type I (NF1) belong to a group of clinically related disorders that share a common pathogenesis, dysregulation of the RAS-MAPK pathway. NS is characterized by short stature, heart defect, pectus deformity and facial dysmorphism, whereas skin manifestations, skeletal defects, Lisch nodules and neurofibromas are characteristic of NF1. Both disorders display considerable clinical variability. Features of NS have been observed in individuals with NF1 -a condition known as neurofibromatosis-Noonan syndrome (NFNS). The major gene causing NFNS is NF1. Rarely, a mutation in PTPN11 in addition to an NF1 mutation is present. We present the clinical and molecular characterization of a family displaying features of both NS and NF1, with complete absence of neurofibromas. To investigate the etiology of the phenotype, mutational analysis of NF1 was conducted, revealing a novel missense mutation in exon 24, p.L1390F, affecting the GAP-domain. Additional RAS-MAPK pathway genes were examined, but no additional mutations were identified. We confirm that NF1 mutations are involved in the etiology of NFNS. Furthermore, based on our results and previous studies we suggest that evaluation of the GAP-domain of NF1 should be prioritized in NFNS. |
| Databáze: | OpenAIRE |
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