title: Mosaic maternal uniparental disomy of chromosome 15 in Prader-Willi syndrome: utility of genome-wide SNP array.
abstract: 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.
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Izumi
authors.forename: Avni B
authors.initials: AB
authors.lastname: Santani
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Deardorff
authors.forename: Holly A
authors.initials: HA
authors.lastname: Feret
authors.forename: Tanya
authors.initials: T
authors.lastname: Tischler
authors.forename: Brian D
authors.initials: BD
authors.lastname: Thiel
authors.forename: Surabhi
authors.initials: S
authors.lastname: Mulchandani
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Stolle
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.forename: Laura K
authors.initials: LK
authors.lastname: Conlin
mesh_terms: D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D016678:Genome; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D046228:Microarray Analysis; D009030:Mosaicism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011218:Prader-Willi Syndrome / Q000175:diagnosis / Q000235:genetics*; D014314:Trisomy; D024182:Uniparental Disomy / Q000235:genetics*; D055517:snRNP Core Proteins / Q000235:genetics
chemical_list: C526417:SNRPN protein, human; D055517:snRNP Core Proteins