Identification and characterization of sporadic and inherited mutations in exon 31 of the neurofibromatosis (NF1) gene.

Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders in humans, and presents with a variety of clinical symptoms, which are highly variable in expression. The mutation rate for NF1 is high, with as many as half of all cases resulting from new mutations. Although the NF1 gene has been cloned and its cDNA sequence determined, the specific role of the NF1 gene product in contributing to the NF1 mutations is one of the first steps in correlating genotype with clinical symptoms of the disease. In this paper we describe two independent mutations in exon 31 of the NF1 gene identified following polymerase chain reaction (PCR) amplification, heteroduplexing, and single strand conformational polymorphism (SSCP) analysis. One is a novel insertion that segregates with the disease phenotype in that particular family (5852insTT), while the other is a further example of the sporadic, recurrent C-->T mutation previously described in the literature (C5842T). The relationship between these mutations and clinical features of NF1 presented by the patients will be discussed.