Large intragenic deletions of the NF2 gene: breakpoints and associated phenotypes.

In this study, the breakpoints of six large intragenic deletions in the NF2 gene are determined, which had initially been detected by multiplex ligation-dependent probe amplification. While one breakpoint occurred within an exon, the remaining 11 lied in the corresponding flanking introns. Two of the deletions were most likely caused by nonallelic homologous recombination between Alu sequences, while the other four appeared to be the result of nonhomologous endjoining, possibly facilitated by rearrangement-promoting elements at the junctions in some cases. The clinical features of patients with large intragenic deletions and individuals with mutations affecting single or multiple nucleotides of the NF2 gene are relatively similar. However, patients with deletions of the 3' exons 15 and 16 of the NF2 gene did exhibit milder phenotypes, especially with respect to the age of disease onset.