Abstract
We describe a young woman with Prader–Willi syndrome (PWS) due to a mosaic imprinting defect. Three independent assays revealed a reduced proportion of nonmethylated SNURF-SNRPN alleles in peripheral blood DNA: methylation-specific PCR followed by denaturing high-performance liquid chromatography (MSP/DHPLC), methylation-sensitive restriction enzyme analysis and methylation-specific real-time PCR analysis. Microsatellite analysis and fluorescence in situ hybridisation revealed apparently normal chromosomes 15 of biparental origin. Based on the MSP/DHPLC and real-time PCR results, we estimate that approximately 50% of the patient's blood cells have an imprinting defect and 50% of the cells are normal. Apart from a rather normal facial appearance, the proband has typical features of PWS.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Horsthemke B, Nazlican H, Husing J et al: Somatic mosaicism for maternal uniparental disomy 15 in a girl with Prader–Willi syndrome: confirmation by cell cloning and identification of candidate downstream genes. Hum Mol Genet 2003; 12: 2723–2732.
Chaddha V, Agarwal S, Phadke SR, Halder A : Low level of mosaicism in atypical Prader–Willi syndrome: detection using fluorescent in situ hybridisation. Indian Pediatr 2003; 40: 166–168.
Buiting K, Gross S, Lich C, Gillessen-Kaesbach G, El-Maarri O, Horsthemke B : Epimutations in Prader–Willi and Angelman syndromes: a molecular study of 136 patients with an imprinting defect. Am J Hum Genet 2003; 72: 571–577.
Baumer A : Analysis of the methylation status of imprinted genes based on methylation-specific polymerase chain reaction combined with denaturing high-performance liquid chromatography. Methods 2002; 27: 139–143.
Baumer A, Wiedemann U, Hergersberg M, Schinzel A : A novel MSP/DHPLC method for the investigation of the methylation status of imprinted genes enables the molecular detection of low cell mosaicisms. Hum Mutat 2001; 17: 423–430.
Zeschnigk M, Boehringer S, Price EA, Onadim Z, Masshöfer L, Lohmann DR : A novel real-time PCR assay for quantitative analysis of methylated alleles (QAMA): analysis of the retinoblastoma locus. Nucl Acids Res 2004; 32: E125.
Nazlican H, Zeschnigk M, Claussen U et al: Somatic mosaicism in patients with Angelman syndrome and an imprinting defect. Hum Mol Genet 2004; 13: 2547–2555.
Cassidy SB, Forsythe M, Heeger S et al: Comparison of phenotype between patients with Prader–Willi syndrome due to deletion 15q and uniparental disomy 15. Am J Med Genet 1997; 68: 433–440.
Gillessen-Kaesbach G, Robinson W, Lohmann D, Kaya-Westerloh S, Passarge E, Horsthemke B : Genotype–phenotype correlation in a series of 167 deletion and non-deletion patients with Prader–Willi syndrome. Hum Genet 1995; 96: 638–643.
Mitchell J, Schinzel A, Langlois S et al: Comparison of phenotype in uniparental disomy and deletion Prader–Willi syndrome: sex specific differences. Am J Med Genet 1996; 65: 133–136.
Robinson WP, Bottani A, Xie YG et al: Molecular, cytogenetic, and clinical investigations of Prader–Willi syndrome patients. Am J Hum Genet 1991; 49: 1219–1234.
Webb T, Whittington J, Clarke D, Boer H, Butler J, Holland A : A study of the influence of different genotypes on the physical and behavioral phenotypes of children and adults ascertained clinically as having PWS. Clin Genet 2002; 62: 273–281.
Saitoh S, Buiting K, Cassidy SB et al: Clinical spectrum and molecular diagnosis of Angelman and Prader–Willi syndrome patients with an imprinting mutation. Am J Med Genet 1997; 68: 195–206.
Gillessen-Kaesbach G, Demuth S, Thiele H, Theile U, Lich C, Horsthemke B : A previously unrecognised phenotype characterised by obesity, muscular hypotonia, and ability to speak in patients with Angelman syndrome caused by an imprinting defect. Eur J Hum Genet 1999; 7: 638–644.
Reik W, Dean W, Walter J : Epigenetic reprogramming in mammalian development. Science 2001; 293: 1089–1093.
Acknowledgements
We are very grateful to our patient and her family for their willingness to collaborate and for consenting to the publication of the data.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wey, E., Bartholdi, D., Riegel, M. et al. Mosaic imprinting defect in a patient with an almost typical expression of the Prader–Willi syndrome. Eur J Hum Genet 13, 273–277 (2005). https://doi.org/10.1038/sj.ejhg.5201337
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.ejhg.5201337
Keywords
This article is cited by
-
Prenatal diagnosis of mosaic chromosomal aneuploidy and uniparental disomy and clinical outcomes evaluation of four fetuses
Molecular Cytogenetics (2023)
-
Prader-Willi syndrome patient with atypical phenotypes caused by mosaic deletion in the paternal 15q11-q13 region: a case report
Italian Journal of Pediatrics (2022)
-
Update of the EMQN/ACGS best practice guidelines for molecular analysis of Prader-Willi and Angelman syndromes
European Journal of Human Genetics (2019)
-
Patients with mosaic methylation patterns of the Prader-Willi/Angelman Syndrome critical region exhibit AS-like phenotypes with some PWS features
Molecular Cytogenetics (2016)
