Molecular Analysis of Chromosome 21 Using Somatic Cell Hybrids a

Down syndrome is the most common specifically identified genetic cause of mental retardation and congenital heart disease in the United States, afflicting one in 700 live-born infants.' In addition, more than 70% of Down syndrome conceptuses may end in spontaneous abortion.2 John Langdon Haydon-Down is credited with first identifying Down syndrome as a unique entity.3 It was first suggested in 19324 that the disease might involve a chromosome defect due to nondisjunction and in 1934 that a trisomy might be invol~ed.~ It was not until 1959, after the correct chromosome number in humans had been determined, that LeJeune was able to show that trisomy of a G-group chromosome was, in fact, associated with Down synd r~me .~ . ' In 1960, the first patient with translocation Down syndrome was described and in 1961 the first case of mosaicism in humans with Down syndrome was Development of banding techniques and the existence of persons with translocation Down syndrome has allowed the pathogenetic region of chromosome 21 to be narrowed down to the band 21q2210,11 and perhaps even to subbands of this regi~n.'~.'"-'~ In some cases in which band q22.1 or band q22.3 was found not to be trisomic, patients were described as having moderate or partial Down syndrome. 13-15 Until definitive biochemical and molecular evidence can be obtained, it is probably most reasonable to consider trisomy