We report here that a child with this form of NF1 displays a heterozygous NF1 gene mutation (c.3721C>T), in addition to a homozygous MLH1 gene mutation (c.676C>T) leading to a truncated MLH1 protein (p.R226X).
Three members of a Portuguese family, who exhibited clinical evidence of neurofibromatosis type 1 (NF1), were found to possess different heritable and pathological mutations in their NF1 genes: a 1.5-Mb deletion spanning the entire NF1 gene, a truncating CGA-->TGA transition in exon 22 (R1241X), and a frameshift mutation in exon 29 (5406insT).
Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain.