RESUMEN
Neurofibromatosis type 1 (NF1) displays overlapping phenotypes with other neurocutaneous diseases such as Legius Syndrome. Here, we present results obtained using a next generation sequencing (NGS) panel including NF1, NF2, SPRED1, SMARCB1, and LZTR1 genes on Ion Torrent. Together with NGS, the Multiplex Ligation-Dependent Probe Amplification Analysis (MLPA) method was performed to rule out large deletions/duplications in NF1 gene; we validated the MLPA/NGS approach using Sanger sequencing on DNA or RNA of both positive and negative samples. In our cohort, a pathogenic variant was found in 175 patients; the pathogenic variant was observed in NF1 gene in 168 cases. A SPRED1 pathogenic variant was also found in one child and in a one year old boy, both NF2 and LZTR1 pathogenic variants were observed; in addition, we identified five LZTR1 pathogenic variants in three children and two adults. Six NF1 pathogenic variants, that the NGS analysis failed to identify, were detected on RNA by Sanger. NGS allows the identification of novel mutations in five genes in the same sequencing run, permitting unambiguous recognition of disorders with overlapping phenotypes with NF1 and facilitating genetic counseling and a personalized follow-up.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Neurofibromatosis 1/genética , Neurofibromina 1/genética , Neurofibromina 2/genética , Factores de Transcripción/genética , Proteínas Adaptadoras Transductoras de Señales/aislamiento & purificación , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mutación/genética , Neurilemoma/diagnóstico , Neurilemoma/genética , Neurilemoma/patología , Neurofibromatosis/diagnóstico , Neurofibromatosis/genética , Neurofibromatosis/patología , Neurofibromatosis 1/diagnóstico , Neurofibromatosis 1/patología , Neurofibromina 1/aislamiento & purificación , Neurofibromina 2/aislamiento & purificación , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Factores de Transcripción/aislamiento & purificación , Adulto JovenRESUMEN
Deletions on chromosome 6q are rarely reported in the literature, and genotype-phenotype correlations are poorly understood. We report a child with a deletion of the 6q21-q22 chromosomal region, providing some intriguing results about the correlation between this region and acro-cardio-facial syndrome, congenital heart disease, split hand and foot malformation, and epilepsy.