[摘要]：Gross deletions of the NF1 gene at 17q11.2 belong to the group of ' genomic disorders' characterized by local sequence architecture that predisposes to genomic rearrangements. Segmental duplications within regions associated with genomic disorders are prone to non-allelic homologous recombination ( NAHR), which mediates gross rearrangements. Copy number variants ( CNVs) without obvious phenotypic consequences also occur frequently in regions of genomic disorders. In the NF1 gene region, putative CNVs have been reportedly detected by array comparative genomic hybridization ( array CGH). These variants include duplications and deletions within the NF1 gene itself ( CNV1) and a duplication that encompasses the SUZ12 gene, the distal NF1-REPc repeat and the RHOT1 gene ( CNV2). To explore the possibility that these CNVs could have played a role in promoting deletion mutagenesis in type- 1 deletions ( the most common type of gross NF1 deletion), non- affected transmitting parents of patients with type- 1 NF1 deletions were investigated by multiplex ligation- dependent probe amplification ( MLPA). However, neither CNV1 nor CNV2 were detected. This would appear to exclude these variants as frequent mediators of NAHR giving rise to type- 1 deletions. Using MLPA, we were also unable to confirm CNV1 in healthy controls as previously reported. We conclude that locus- specific techniques should be used to independently confirm putative CNVs, originally detected by array CGH, to avoid false- positive results. In one patient with an atypical deletion, a duplication in the region of CNV2 was noted. This duplication could have occurred concomitantly with the deletion as part of a complex rearrangement or may alternatively have preceded the deletion.
