A LARGE FAMILY WITH SUBTELOMERIC TRANSLOCATION T(18-21)(Q23-Q22.1) AND MOLECULAR BREAKPOINT IN THE DOWN-SYNDROME CRITICAL REGION

We describe a 17-month-old infant with clinical features of Down syndr ome and a normal karyotype by standard chromosomal analysis, her two u ncles aged 28 and 30 years, respectively, with reduced intelligence an d unusual appearance but not apparent Down syndrome, and a severely re tarded 6-year-old girl with dysmorphy and epilepsy from the same famil y. Cytogenetic studies of patients and normal intervening relatives ha d been carried out at different institutions with normal results. Fluo rescence in situ hybridization using whole chromosome painting and uni que-copy probes (cosmids) and high-resolution banding revealed a famil ial subtelomeric translocation of chromosomes 18 and 21, resulting in partial trisomy 21 in the infant and her two uncles, and partial monos omy 21 in the 6-year-old girl, Cytogenetic breakpoints were located in bands 18q23 and 21q22.1, respectively. The molecular breakpoint on ch romosome 21 was located between D21S211 (proximal) and D21S1283 (dista l) and thus maps within the Down syndrome critical region.