NF1 single and multi-exons copy number variations in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is caused by dominant loss-of-function mutations of the tumor suppressor NF1 containing 57 constitutive coding exons. A huge number of different pathogenic NF1 alterations has been reported. The aim of the present study was to evaluate the usefulness of a multiplex ligation-dependent probe amplification (MLPA) approach in NF1 patients to detect single and multi-exon NF1 gene copy number variations. A genotype-phenotype correlation was then performed in NF1 patients carrying these types of genetic alterations. Among 565 NF1 index cases from the French NF1 cohort, single and multi-exon deletions/duplications screening identified NF1 partial deletions/duplications in 22 patients (~4%) using MLPA analysis. Eight single exon deletions, 11 multiple exons deletions, 1 complex rearrangement and 2 duplications were identified. All results were confirmed using a custom array-CGH. MLPA and custom array-CGH allowed the identification of rearrangements that were missed by cDNA/DNA sequencing or microsatellite analysis. We then performed a targeted next-generation sequencing of NF1 that allowed confirmation of all 22 rearrangements. No clear genotype-phenotype correlations were found for the most clinically significant disease features of NF1 in patients with single and multi-exons NF1 gene copy number changes.

NF1 molecular characterization and neurofibromatosis type I genotype-phenotype correlation: the French experience.

Neurofibromatosis type 1 (NF1) affects about one in 3,500 people in all ethnic groups. Most NF1 patients have private loss-of-function mutations scattered along the NF1 gene. Here, we present an original NF1 investigation strategy and report a comprehensive mutation analysis of 565 unrelated patients from the NF-France Network. A NF1 mutation was identified in 546 of the 565 patients, giving a mutation detection rate of 97%. The combined cDNA/DNA approach showed that a significant proportion of NF1 missense mutations (30%) were deleterious by affecting pre-mRNA splicing. Multiplex ligation-dependent probe amplification allowed the identification of restricted rearrangements that would have been missed if only sequencing or microsatellite analysis had been performed. In four unrelated families, we identified two distinct NF1 mutations within the same family. This fortuitous association points out the need to perform an exhaustive NF1 screening in the case of molecular discordant-related patients. A genotype-phenotype study was performed in patients harboring a truncating (N = 368), in-frame splicing (N = 36), or missense (N = 35) mutation. The association analysis of these mutation types with 12 common NF1 clinical features confirmed a weak contribution of the allelic heterogeneity of the NF1 mutation to the NF1 variable expressivity.

A influência do toque no cuidado às crianças especiais / La influencia del tacto en el cuidado a los niños con necesidades especiales / The influence of touch in caring for special children

Objetivo: identificar a influência de toque no cuidado às crianças com necessidades especiais na percepção dos trabalhadores. Método: pesquisa qualitativa em que fizeram parte da investigação oito profissionais de um Centro de Integração à Criança Especial do Município de Porto Alegre, Rio Grande do Sul. Para interpretação dos dados,utilizou-se a análise de conteúdo. Resultados: originaram-se as categorias percepção dos cuidadores em relação à influência do toque como instrumento de comunicação entre acriança especial e o profissional; percepção dos cuidadores em relação à influência do toque no bem-estar da criança especial e percepção dos cuidadores em relação à influência do toque na reabilitação da criança especial. Conclusões: os resultados evidenciaram que o toque é uma ferramenta que influencia no bem-estar das crianças e caracteriza-se por ser um instrumento de comunicação alternativa e, modo de aproximação entre o profissional e a criança, possibilitando a criação de um vínculo positivo e consequentemente, favorecendo o processo de reabilitação.

Aim: to identify the influence of touching in the process of caring for childrenwith special needs in the perception health professionals. Method: the sample consistedof eight professionals of the Integration Center for Children with Special Needs in PortoAlegre, Rio Grande do Sul. Results: the content analysis arose the following categories:perceptions of caregivers with regards the influence of touch as a communication toolbetween the special child and the professional; the perception of the caregivers regardingthe influence of touch on the welfare of the child and the perception of the caregiverregarding the influence of touch on the rehabilitation of the special child. Conclusions: the results showed that touch is a tool that influences the well-being of children and isportrayed by being a communication tool that approach the professionals into thechildren, enabling the creation of a positive bond and favoring the rehabilitation.

Objetivo: identificar la influencia del tacto en el cuidado de niños en lapercepción de los profesionales de la salud. Método: investigación cualitativa, realizada conocho profesionales de un Centro de Integração à Criança Especial en Porto Alegre, RS. Para lainterpretación de los datos fue utilizado el análisis de contenido. Resultados: percepción decuidadores con relación a la influencia del tacto como instrumento de comunicación entre elniño especial y el profesional; percepción de los cuidadores con relación a la influencia deltacto en el bienestar del niño y la percepción de los cuidadores con relación a la influencia deltacto en la rehabilitación del niño. Conclusiones: fue evidenciado que el tacto es unaherramienta que influencia en el bienestar de niños y se caracteriza por ser un instrumentode comunicación alternativa y de aproximación entre el profesional y el niño, creando unvínculo positivo y favoreciendo consecuentemente el proceso de rehabilitación.