The impact of imprinting: Prader-Willi syndrome resulting from chromosome translocation, recombination, and nondisjunction
- Oregon Health Sciences Univ., Portland, OR (United States); and others
Prader-Willi syndrome (PWS) is most often the result of a deletion of bands q11.2-q13 of the paternally derived chromosome 15, but it also occurs either because of maternal uniparental disomy (UPD) of this region or, rarely, from a methylation imprinting defect. A significant number of cases are due to structural rearrangements of the pericentromeric region of chromosome 15. We report two cases of PWS with UPD in which there was a meiosis I nondisjunction error involving an altered chromosome 15 produced by both a translocation event between the heteromorphic satellite regions of chromosomes 14 and 15 and recombination. In both cases, high-resolution banding of the long arm was normal, and FISH of probes D15S11, SNRPN, D15S10, and GABRB3 indicated no loss of this material. Chromosome heteromorphism analysis showed that each patient had maternal heterodisomy of the chromosome 15 short arm, whereas PCR of microsatellites demonstrated allele-specific maternal isodisomy and heterodisomy of the long arm. SNRPN gene methylation analysis revealed only a maternal imprint in both patients. We suggest that the chromosome structural rearrangements, combined with recombination in these patients, disrupted normal segregation of an imprinted region, resulting in uniparental disomy and PWS. 30 refs., 6 figs., 1 tab.
- OSTI ID:
- 273500
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 5 Vol. 58; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
CHROMOSOMAL ABERRATIONS
DNA HYBRIDIZATION
FLUORESCENCE
GENE RECOMBINATION
GENES
GENETIC MAPPING
GENETICS
HEREDITARY DISEASES
HUMAN CHROMOSOME 14
HUMAN CHROMOSOME 15
METHYLATION
NON-DISJUNCTION
PATIENTS
POLYMERASE CHAIN REACTION
PROBES
STRUCTURE-ACTIVITY RELATIONSHIPS