Alternate centromere inactivation in a pseudodicentric (15;20)(pter;pter) associated with a progressive neurological disorder

• Published in: Journal of medical genetics Vol. 26; no. 10; pp. 626 - 630
• Main Authors: Rivera, H, Zuffardi, O, Maraschio, P, Caiulo, A, Anichini, C, Scarinci, R, Vivarelli, R
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01-10-1989; BMJ; BMJ Publishing Group LTD
• Subjects: Adolescent; Biological and medical sciences; Centromere - pathology; Chromosome aberrations; Chromosome Banding; Chromosomes - pathology; Fibroblasts - ultrastructure; Fluorescent Antibody Technique; Humans; Karyotyping; Lymphocytes - ultrastructure; Male; Medical genetics; Medical sciences; Metaphase - genetics; nervous system diseases; Nervous System Diseases - genetics; Chromosomal aberration; Human; Nervous system diseases; Melting; Dicentric chromosome; Inactivation; Telomer; Abnormal F20 chromosome; Centromere; Cytogenetics; Abnormal chromosome; Degenerative disease; Abnormal «D15» chromosome; Child
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.26.10.626

A 13 year old male with a severe progressive neurological disorder was found to have a pseudodicentric chromosome resulting from a telomeric fusion 15p;20p. In lymphocytes, the centromeric constriction of the abnormal chromosome was always that of the chromosome 20, while in fibroblasts both centromeres were alternately constricted. Cd staining was positive only at the active centromere, but a weak anticentromere immunofluorescence was present at the inactive one. We suggest that centromere inactivation results from a modified conformation of the functional DNA sequences preventing normal binding to centromere specific proteins. We also postulate that the patient's disorder, reminiscent of a spongy glioneuronal dystrophy as seen in Alper's and Creutzfeldt-Jakob diseases, may be secondary to the presence of the pathogenic isoform of the prion protein encoded by a gene mapped to 20p12---pter.