Molecular analysis of three Down syndrome patients with a "mirror" duplication of chromosome 21

C. Pangalos12, D. Theophile13, P.M. Sinet3, D. Abazis2, Z. Chettouh3, M.O. Rethoré1, M. Prieur1, C. Verelen4, J. Lejeune1 and J.M. Delabar3

Am. J. Hum. Genet. 1989, 45, abstr. A86(0331), 1.178


Phenotypic, cytogenetic and molecular analysis were performed in three patients: AL, TY and LI. All had the phenotypic features of Down syndrome. In patient TY, two signs were discordant: ears with a large unfolded helix and post-natal hypertonia. In the 3 patients, karyotypic analysis by high resolution R banding showed a "mirror" duplication of chromosome 21: 46, XX or XY, -21, + psu dic(21)t(21;21)(q22.3;q22.3). The evaluation of the copy number of chromosome 21 single-copy sequences was performed by a slot blot method. In patient AL, SOD1, D21S16, PFKL and CD18 were all found in 3 copies. In patient TY, the copy number for SOD1, D21S15 and CD18 was respectively 3, 3 and 1. In patient LI, the copy number for D21S15, BCEI and CD18 was respectively 3, 3 and 1. These results indicate that: 1- the translocation leading to "mirror" duplication of chromosome 21 lies within 21q22.3 as showed by the cytogenetic analysis; 2- the location of the translocation breakpoint is variable: distal to CD18 in patient AL, proximal to CD18 in patients TY and LI; 3- this type of chromosome rearragement may lead to partial deletion of 21q22.3. As patient TY shows some clinical features not usually encountered in trisomy 21, further molecular analysis of these and other patients with "mirror" duplication of chromosome 21 may be relevant to phenolype-genotype correlation studies in Down syndrome.