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Title: Mutational spectrum by phenotype: panel-based NGS testing of patients with clinical suspition of RASopathy and children with multiple café-au-lait macules
Author: Castellanos, Elisabeth
Rosas, Inma
Negro, Alex
Gel Moreno, Bernat
Alibés, Andreu
Baena, Neus
Pineda Marfà, Mercè
Pi, Graciela
Pintos, Guillem
Salvador, Hector
Lázaro García, Conxi
Blanco Guillermo, Ignacio
Vilageliu i Arqués, Lluïsa
Brems, Hilde
Grinberg Vaisman, Daniel Raúl
Legius, Eric
Serra Arenas, Eduard
Keywords: Malalties hereditàries
Genetic diseases
Issue Date: 1-Oct-2019
Publisher: John Wiley & Sons
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
Note: Versió postprint del document publicat a:
It is part of: Clinical Genetics, 2019, vol. 97, p. 264-275
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ISSN: 0009-9163
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

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