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Mutational spectrum by phenotype: panel-based NGS testing of patients with clinical suspicion of RASopathy and children with multiple café-au-lait macules
- Source :
- CLINICAL GENETICS, r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu, Fundació Sant Joan de Déu, Dipòsit Digital de la UB, Universidad de Barcelona, Clinical Genetics, r-IGTP: Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol, Institut de Recerca Germans Trias i Pujol (IGTP), r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu, instname, r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol
- Publication Year :
- 2020
- Publisher :
- WILEY-BLACKWELL, 2020.
-
Abstract
- Children with neurofibromatosis type 1 (NF1) may exhibit an incomplete clinical presentation, making difficult to reach a clinical diagnosis. A phenotypic overlap may exist in children with other RASopathies or with other genetic conditions if only multiple café-au-lait macules (CALMs) are present. The syndromes that can converge in these inconclusive phenotypes have different clinical courses. In this context, an early genetic testing has been proposed to be clinically useful to manage these patients. We present the validation and implementation into diagnostics of a custom NGS panel (I2HCP, ICO-IMPPC Hereditary Cancer Panel) for testing patients with a clinical suspicion of a RASopathy (n = 48) and children presenting multiple CALMs (n = 102). We describe the mutational spectrum and the detection rates identified in these two groups of individuals. We identified pathogenic variants in 21 out of 48 patients with clinical suspicion of RASopathy, with mutations in NF1 accounting for 10% of cases. Furthermore, we identified pathogenic mutations mainly in the NF1 gene, but also in SPRED1, in more than 50% of children with multiple CALMs, exhibiting an NF1 mutational spectrum different from a group of clinically diagnosed NF1 patients (n = 80). An NGS panel strategy for the genetic testing of these two phenotype-defined groups outperforms previous strategies.
- Subjects :
- 0301 basic medicine
Male
multiple CALMs
DNA Mutational Analysis
neurofibromatosis type 1
030105 genetics & heredity
Malalties hereditàries
Medicine
Child
Children
Genetics (clinical)
Neurofibromin 1
medicine.diagnostic_test
Cafe-au-Lait Spots
High-Throughput Nucleotide Sequencing
genetic testing
Phenotype
Cafe-au-lait macules
Neoplasm Proteins
Child, Preschool
Hereditary Cancer
Female
Infants
Genetic diseases
medicine.medical_specialty
Neurofibromatosis 1
Context (language use)
RASopathy
NGS panel
03 medical and health sciences
Genetics
Humans
Genetic Testing
Neurofibromatosis
RASopathies
Genetic testing
business.industry
Infant
Proteins
medicine.disease
Dermatology
030104 developmental biology
Early Diagnosis
Clinical diagnosis
Mutation
business
Proteïnes
Subjects
Details
- ISSN :
- 00099163
- Database :
- OpenAIRE
- Journal :
- CLINICAL GENETICS, r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu, Fundació Sant Joan de Déu, Dipòsit Digital de la UB, Universidad de Barcelona, Clinical Genetics, r-IGTP: Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol, Institut de Recerca Germans Trias i Pujol (IGTP), r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu, instname, r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol
- Accession number :
- edsair.doi.dedup.....f0919872b015311500d26be16d974edd