Mendelian cytogenetics. Chromosome rearrangements associated with mendelian disorders.

The first successful mapping of a mendelian disorder by chromosome rearrangements was that of the Duchenne muscular dystrophy locus to Xp21.1-5 Since then, chromosome ab- errations which delete, truncate, or otherwise rearrange and mutate specific genes have not only helped in the mapping of other disease loci,6 but have turned out to be key elements for the rapid isolation of disease genes by positional cloning strategies.7 Accordingly, a listing of the clinical disorders in which associated chromosome rearrangements have been described forms a part of the Human Gene Mapping Workshops.6 Although the early suc- cess led to a proposal for systematic cytogene- tic analysis of subjects with mendelian dis- orders,8 this has rarely been done. A common feeling is that, as mutations, these rearrange- ments are rare exceptions. The aim of the present review is to document that they may be rare, but are not exceptions, and to focus on factors which may influence their occurrence and facilitate their detection.