A CLINICAL AND MOLECULAR STUDY OF MOSAICISM FOR TRISOMY-17

Trisomy 17 has never been reported in a live birth. We present a case of mosaic trisomy 17 in a male presenting with mental retardation, sei zures, attention deficit hyperactivity and autistic disorders, hearing loss, growth retardation, microcephaly, and minor anomalies. Although peripheral blood lymphocyte chromosomes were normal, trisomy 17 was p resent in the skin fibroblasts. The percentage of abnormal cells appea rs to have increased from 18% in an initial skin biopsy at age 3 years 8 months to 80% at age 8 years 8 months. Molecular analysis using 13 highly polymorphic markers spanning the length of chromosome 17 demons trated the extra chromosome 17 in the skin to be of paternal origin. T hree alleles were never seen in the trisomic cell line, suggesting tha t the extra chromosome arose through a mitotic duplication error after conception. Uniparental disomy was excluded in the euploid blood samp le. Although Smith-Magenis syndrome involves a deletion of proximal 17 p, some of the clinical features of this mosaic trisomy 17 patient, su ch as decreased REM sleep and increased tolerance to pain, are suggest ive of phenotypic features observed in Smith-Magenis syndrome. We spec ulate that there are dosage-sensitive genes located in 17p11.2 that pr oduce these phenotypes for either deficiencies or overexpression of th eir gene products.