Familial

It is apparent from several studies that there is a familial clustering of cases of CLL, perhaps in as many as 5% of cases.8'9 The pedigrees are not normally large, usually affecting only two generations. The genetic defect(s) underlying the familial form of the disease remain unknown but are now the subject of a number of epidemiologic and molecular studies. A number of "candidate genes" have been investigated, but none has shown involvement. Application of whole genomic techniques to these cases may allow identification of the key gene(s). Conventional comparative genomic hybridization has been used in order to identify regions of recurrent genomic loss in DNA from patients with familial CLL; four areas of loss were identified, including Xp11.2-p21, Xq21-qter, 2p12-p14, and 4q11-q21.10 Use of bacterial artificial chromosomes (BAC) arrays would greatly enhance the resolution of this analysis.11

Cases may show anticipation, with both generations often presenting concurrently; whether this reflects trinucleotide expansion, as seen in neurological disorders that exhibit this phenomenon (increasing expansion being associated with an earlier age of onset of disease), is not yet clear. However, anticipation is not a feature of all series and may reflect ascertainment bias.

Please see http://www.icr.ac.uk for further information and how to enter families into an international collaborative study.

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