The impact of imprinting: Prader-Willi syndrome resulting from chromosome translocation, recombination, and nondisjunction

Suellen Toth-Fejel, Susan Olson, Kristine Gunter, Franklin Quan, Jan Wolford, Bradley W. Popovich, R. Ellen Magenis

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1008-1016
Number of pages9
JournalAmerican Journal of Human Genetics
Volume58
Issue number5
StatePublished - Apr 26 1996

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Toth-Fejel, S., Olson, S., Gunter, K., Quan, F., Wolford, J., Popovich, B. W., & Ellen Magenis, R. (1996). The impact of imprinting: Prader-Willi syndrome resulting from chromosome translocation, recombination, and nondisjunction. American Journal of Human Genetics, 58(5), 1008-1016.