Molecular and cytogenetic investigation of complex tissue-specific duplication and loss of chromosome 21 in a child with a monosomy 21 phenotype.

Several recent molecular studies have suggested that the clinical phenotype of Down syndrome may be due to triplication of 21q22 [McCormick et al., 1989] as initially suggested by Niebuhr [1974], and perhaps just 21q22.2 [Korenberg et al., 1989, 1990; Rahmani et al., 1989]. Recently, we studied a patient with a phenotype inconsistent with Down syndrome, whose lymphocyte karyotype on several occasions detected only 46,XX,-21, + dic(21)(qter----p11::p11----qter). Combined karyotype and molecular studies on both lymphocytes and fibroblasts allowed correct identification of the abnormality as a complex monosomy/trisomy 21 mosaicism involving a marker derived from idic (21) (p11), and probable assignment of a maternal origin for the error(s). The patient's phenotype was found to be most consistent with monosomy 21. Detailed study of our patient underscores (1) the need for confirmation that there is phenotype/karyotype correlation and (2) the usefulness of molecular analyses to complement the cytogenetic interpretation of marker chromosomes.