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

Alessandra B Trovó,Eloiza H Tajara,Walter F De Azevedo Jr,Eny M Goloni-Bertollo,Ulises M Mancini,Paula Rahal

doi:10.1590/s1415-47572004000300003

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.

Highlights

Neurofibromatosis type 1 is one of the most common autosomal dominant disorders, affecting approximately 1:3,000 individuals
The Neurofibromatosis type 1 (NF1) gene, mapped to 17q11.2 (Barker et al, 1987), contains 60 exons and has one of the highest mutation rates described for human genes (Huson and Hughes, 1994)
Mutations in the GTPase-activating protein (GAP)-related domain in lung cancer samples have been screened by Furukawa et al (2003) using single-strand conformation polymorphism (SSCP) and sequencing, with a mutation and polymorphism detection rate of 8%

Summary

Introduction

Neurofibromatosis type 1 is one of the most common autosomal dominant disorders, affecting approximately 1:3,000 individuals. The main characteristics of the disease comprise multiple neurofibromas, cafe-au-lait skin spots, Lisch nodules and freckling, but, in a minority of patients, other features, such as scoliosis, macrocephaly, short stature, malignancies, and learning disabilities, are found (Huson and Hughes, 1994). Mutations in the GAP-related domain in lung cancer samples have been screened by Furukawa et al (2003) using SSCP and sequencing, with a mutation and polymorphism detection rate of 8%.

Results

Conclusion