How to Cite this Article: Izumi K, Santani AB, Deardorff MA, Feret HA, Tischler T, Thiel BD, Mulchandani S, Stolle CA, Spinner NB, Zackai EH, Conlin LK. 2012. Mosaic maternal uniparental disomy of chromosome 15 in Prader–Willi syndrome: Utility of genome-wide SNP array. Am J Med Genet Part A 161A:166–171.
Mosaic maternal uniparental disomy of chromosome 15 in Prader–Willi syndrome: Utility of genome-wide SNP array†
Article first published online: 7 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 1, pages 166–171, January 2013
How to Cite
Izumi, K., Santani, A. B., Deardorff, M. A., Feret, H. A., Tischler, T., Thiel, B. D., Mulchandani, S., Stolle, C. A., Spinner, N. B., Zackai, E. H. and Conlin, L. K. (2013), Mosaic maternal uniparental disomy of chromosome 15 in Prader–Willi syndrome: Utility of genome-wide SNP array. Am. J. Med. Genet., 161: 166–171. doi: 10.1002/ajmg.a.35625
- Issue published online: 22 DEC 2012
- Article first published online: 7 DEC 2012
- Manuscript Accepted: 25 JUL 2012
- Manuscript Received: 12 APR 2012
- post-fertilization error;
- trisomy rescue;
- imprinting disorder
Prader–Willi syndrome is caused by the loss of paternal gene expression on 15q11.2–q13.2, and one of the mechanisms resulting in Prader–Willi syndrome phenotype is maternal uniparental disomy of chromosome 15. Various mechanisms including trisomy rescue, monosomy rescue, and post fertilization errors can lead to uniparental disomy, and its mechanism can be inferred from the pattern of uniparental hetero and isodisomy. Detection of a mosaic cell line provides a unique opportunity to understand the mechanism of uniparental disomy; however, mosaic uniparental disomy is a rare finding in patients with Prader–Willi syndrome. We report on two infants with Prader–Willi syndrome caused by mosaic maternal uniparental disomy 15. Patient 1 has mosaic uniparental isodisomy of the entire chromosome 15, and Patient 2 has mosaic uniparental mixed iso/heterodisomy 15. Genome-wide single-nucleotide polymorphism array was able to demonstrate the presence of chromosomally normal cell line in the Patient 1 and trisomic cell line in Patient 2, and provide the evidence that post-fertilization error and trisomy rescue as a mechanism of uniparental disomy in each case, respectively. Given its ability of detecting small percent mosaicism as well as its capability of identifying the loss of heterozygosity of chromosomal regions, genome-wide single-nucleotide polymorphism array should be utilized as an adjunct to the standard methylation analysis in the evaluation of Prader–Willi syndrome. © 2012 Wiley Periodicals, Inc.