MOLECULAR ANALYSIS OF CHROMOSOME-21 IN A PATIENT WITH A PHENOTYPE OF DOWN-SYNDROME AND APPARENTLY NORMAL KARYOTYPE

Down syndrome (DS) is caused in most cases by the presence of an extra chromosome 21. It has been shown that the DS phenotype is produced by duplication of only a small part of the long arm of chromosome 21, th e 21q22 region, including and distal to locus D21S55. We present molec ular investigations on a woman with clinically typical DS but apparent ly normal chromosomes. Her parents were consanguineous and she had a s ister with a DS phenotype, who died at the age of 15 days. Repeated cy togenetic investigations (G-banding and high resolution banding) on th e patient and her parents showed apparently normal chromosomes. Autora diographs of quantitative Southern blots of DNAs from the patient, her parents, trisomy 21 patients, and normal controls were analyzed after hybridization with unique DNA sequences regionally mapped on chromoso me 21. Sequences D21S59, D21S1, D21S11, D21S8, D21S17,D21S55, ERG, D21 S15, D21S112, and COL6A1 were all found in two copies. Fluorescent in situ hybridization with a chromosome 21-specific genomic library showe d no abnormalities and only two copies of chromosome 21 were detected. Nineteen markers from the critical region studied with polymerase cha in reaction amplification of di- and tetranucleotide repeats did not i ndicate any partial trisomy 21. From this study we conclude that the p atient does not have any partial submicroscopic trisomy for any segmen t of chromosome 21. It seems reasonable to assume that she suffers fro m an autosomal recessive disorder which is phenotypically indistinguis hable from DS. (C) 1996 Wiley-Liss, Inc.