Other Candidate CLL Predisposition Genes

Linkage of Hodgkin's disease to the pseudoautosomal region of the genome has recently been proposed by Horwitz and Wiernik (37) on the basis of an excess of sex concordance among affected siblings. The common lineage of Hodgkin's disease and CLL prompted us to examine whether familial CLL also shows pseudoautosomal linkage. An analysis of published CLL families shows that the frequency of sex-concordant sib pairs is skewed beyond random expectation; however, it is impossible to preclude publication bias, and so the implicated pseudoautosomal linkage in CLL is questionable (38).

In a number of mendelian diseases anticipation has been shown to be indicative of a dynamic mutation mechanism involving expansion of triplet repeat motifs (39). If the genetic basis of familial CLL involves a similar mechanism, this offers a novel method of identifying a predisposition locus for the disease since specialized methods exist specifically for cloning genes associated with such expansions (40).

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