A severe form of Noonan syndrome and autosomal dominant café-au-lait spots - evidence for different genetic origins
Autor: | Marie-Louise Bondeson, Anna-Maja Nyström, Bo Strömberg, Ann-Charlotte Thuresson, Gerd Holmström, Göran Annerén, Sara Ekvall |
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Rok vydání: | 2009 |
Předmět: |
Adult
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Candidate gene Genotype Genetic Linkage DNA Mutational Analysis Protein Tyrosine Phosphatase Non-Receptor Type 11 Gene mutation Young Adult Café au lait spot Genes Neurofibromatosis 1 medicine Humans Family Genetic Predisposition to Disease Neurofibromatosis Adaptor Proteins Signal Transducing Genetics business.industry Cafe-au-Lait Spots Noonan Syndrome Intracellular Signaling Peptides and Proteins Membrane Proteins General Medicine medicine.disease Repressor Proteins PTPN11 Phenotype Mutation Pediatrics Perinatology and Child Health Mutation (genetic algorithm) Noonan syndrome Medical genetics Female medicine.symptom business |
Zdroj: | Acta Paediatrica. 98:693-698 |
ISSN: | 1651-2227 0803-5253 |
Popis: | Aim: The clinical overlap among Noonan syndrome (NS), cardio-facio-cutaneous (CFC), LEOPARD and Costello syndromes as well as Neurofibromatosis type 1 is extensive, which complicates the process of diagnosis. Further genotype-phenotype correlations are required to facilitate future diagnosis of these patients. Therefore, investigations of the genetic cause of a severe phenotype in a patient with NS and the presence of multiple cafspots (CAL) spots in the patient and four members of the family were performed. Methods: Mutation analyses of candidate genes, PTPN11, NF1, SPRED1 and SPRED2, associated with these syndromes, were conducted using DNA sequencing. Results: A previously identified de novo mutation, PTPN11 F285L and an inherited NF1 R1809C substitution in the index patient were found. However, neither PTPN11 F285L, NF1 R1809C, SPRED1 nor SPRED2 segregated with CAL spots in the family. The results indicate that the familial CAL spots trait in this family is caused by a mutation in another gene, distinct from previous genes associated with CAL spots in these syndromes. Conclusion: We suggest that the atypical severe symptoms in the index patient may be caused by an additive effect on the F285L mutation in PTPN11 by another mutation, for example the NF1 R1809C or alternatively, the not yet identified gene mutation associated with CAL spots in this family. |
Databáze: | OpenAIRE |
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