RESUMO
The genetic basis of familial CLL is poorly understood and to date no gene which when mutated in the germline has been unambiguously shown to confer susceptibility to the disease. Dok1 maps to chromosome 2p13, a region commonly rearranged in CLL. Dok1 inhibits MAP kinase activity, down-regulates cell proliferation and has a suppressive effect on cellular transformation and B-cell signalling pathways. A recent report has implicated mutation of Dok1 in the aetiology of CLL. To examine the proposition that germline mutations in Dok1 act as high penetrance susceptibility alleles for CLL we screened 140 familial cases for functional sequence variants. No pathogenic mutations were detected. This result indicates that germline mutations in Dok1 are unlikely to cause an inherited predisposition to CLL.
