Mutational analysis of the GAP-related domain of the neurofibromatosis type 1 gene in Brazilian NF1 patients

Abstract

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder caused by mutations in the NF1 gene. In the present study, a total of 55 unrelated NF1 patients were screened for mutations in the GAP-related domain/GRD (exons 20-27a) by single-strand conformation polymorphism (SSCP). Four different mutations were identified and, taken together, they comprise one nonsense substitution (Q1189X), one deletion (3525-3526delAA), one missense substitution (E1356G) and one mutation in the splice acceptor site (c.4111-1G>A). One novel polymorphism (c.4514+11C>G) and other three putative polymorphisms were also found (c.3315-27G>A, V1146I and V1317A). Genotype-phenotype correlations were investigated, but no particular association was detected.

High frequencies of plexiform neurofibromas, mental retardation, learning difficulties, and scoliosis in Brazilian patients with neurofibromatosis type 1

“…The NIH criteria include at least two of the following findings: 6 or more café-au-lait spots larger than 5 mm in diameter in prepubertal subjects and larger than 15 mm in postpubertal subjects, 2 or more neurofibromas or 1 plexiform neurofibroma, intertriginous freckling, distinctive bone lesions (sphenoid wing dysplasia or pseudoarthrosis), 2 or more Lisch nodules, an optic glioma, or a first-degree relative diagnosed with NF1. Samples from these patients were previously analyzed by molecular biology techniques and the data were recently published (9).…”

Neurofibromatosis tipo 1 (NF1) y su diagnóstico molecular como estrategia del diagnóstico diferencial y a edades tempranas

“…Otros estudios mostraron porcentajes similares 4,5% 66 , o aproximados 11% 22 , 1,59% 69 . Herramientas y bases de datos bioinformáticas han sido utilizadas para caracterizar mutaciones en NF1: para el modelado molecular 60,64 , diseño de oligonucleótidos 64,65 y determinación de mutaciones 22,40,69 . En la actualidad se utilizan herramientas computacionales para determinar los mecanismos de errores de empalme, la patogenicidad de las mutaciones y el alineamiento de proteínas 69 .…”