title: Detection of mutually exclusive mosaicism in a girl with genotype-phenotype discrepancies.
abstract: Discordance between clinical phenotype and genotype has multiple causes, including mosaicism. Phenotypes can be modified due to tissue distribution, or the presence of multiple abnormal cell lines with different genomic contributions. We have studied a 20-month-old female whose main phenotypes were failure to thrive, developmental delay, and patchy skin pigmentation. Initial chromosome and SNP microarray analysis of her blood revealed a non-mosaic ∼24 Mb duplication of 15q25.1q26.3 resulting from the unbalanced translocation of terminal 15q to the short arm of chromosome 15. The most common feature associated with distal trisomy 15q is prenatal and postnatal overgrowth, which was not consistent with this patient's phenotype. The phenotypic discordance, in combination with the patchy skin pigmentation, suggested the presence of mosaicism. Further analysis of skin biopsies from both hyper- and hypopigmented regions confirmed the presence of an additional cell line with the short arm of chromosome X deleted and replaced by the entire long arm of chromosome 15. The Xp deletion, consistent with a variant Turner Syndrome diagnosis, better explained the patient's phenotype. Parental studies revealed that the alterations in both cell lines were de novo and the duplicated distal 15q and the deleted Xp were from different parental origins, suggesting a mitotic event. The possible mechanism for the occurrence of two mutually exclusive structural rearrangements with both involving the long arm of chromosome 15 is discussed.
authors.affiliation: Department of Pathology & Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Minjie
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Pathology & Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Surabhi
authors.initials: S
authors.lastname: Mulchandani
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Dubbs
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Daniel
authors.initials: D
authors.lastname: Swarr
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Louise
authors.initials: L
authors.lastname: Pyle
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.affiliation: Department of Pathology & Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
authors.affiliation: Department of Pathology & Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Conlin
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D020440:Gene Duplication; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D009030:Mosaicism / Q000196:embryology*; D010641:Phenotype; D011296:Prenatal Diagnosis; D011379:Prognosis; D014314:Trisomy / Q000175:diagnosis / Q000235:genetics*
keywords: SNP microarray analysis; Xp deletion; distal 15q duplication; tissue specific mosaicism