title: Utility of SNP arrays in detecting, quantifying, and determining meiotic origin of tetrasomy 12p in blood from individuals with Pallister-Killian syndrome.
abstract: Identification of the isochromosome 12p (i(12p)) associated with Pallister-Killian syndrome is complicated by the low frequency of this supernumerary chromosome in PHA stimulated peripheral blood lymphocytes, and frequently requires cytogenetic analysis of fibroblast cells. Recently, it has been shown that array CGH techniques are able to detect tetrasomy 12p in peripheral blood, even when not identified by traditional cytogenetic techniques. We studied 15 patients with a previous cytogenetic and clinical diagnosis of Pallister-Killian syndrome using genome-wide SNP arrays to investigate the ability of this platform to identify the i(12p) in blood and tissue. Array analysis verified tetrasomy 12p in all samples from fibroblasts, but was only able to detect it in 46% of blood samples. The genotyping information available from the SNP arrays allowed for the detection of as low as 5% mosaicism, as well as suggesting a Meiosis II origin for the isochromosome in the majority of patients. Analysis of the percentage of abnormal cells with patient age at time of study suggests that the frequency of the i(12p) decreased with age in blood, but not in fibroblasts. These highlight the power of SNP arrays in detecting and characterizing the isochromosome 12p in Pallister-Killian syndrome as well as underscoring the important utility of traditional cytogenetic techniques.
authors.affiliation: Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19146, USA. conlinl@email.chop.edu
authors.forename: Laura K
authors.initials: LK
authors.lastname: Conlin
authors.forename: Maninder
authors.initials: M
authors.lastname: Kaur
authors.forename: Kosuke
authors.initials: K
authors.lastname: Izumi
authors.forename: Lindsey
authors.initials: L
authors.lastname: Campbell
authors.forename: Alisha
authors.initials: A
authors.lastname: Wilkens
authors.forename: Dinah
authors.initials: D
authors.lastname: Clark
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Deardorff
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.forename: Phillip
authors.initials: P
authors.lastname: Pallister
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
mesh_terms: D002675:Child, Preschool; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D020732:Cytogenetic Analysis / Q000379:methods; D005347:Fibroblasts / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018404:Isochromosomes / Q000235:genetics; D008540:Meiosis / Q000235:genetics*; D009030:Mosaicism; D020641:Polymorphism, Single Nucleotide; D058670:Tetrasomy / Q000175:diagnosis / Q000235:genetics*