title: Copy number variation analysis in 98 individuals with PHACE syndrome.
abstract: PHACE syndrome is the association of large segmental facial hemangiomas and congenital anomalies, such as posterior fossa malformations, cerebral arterial anomalies, coarctation of the aorta, eye anomalies, and sternal defects. To date, the reported cases of PHACE syndrome have been sporadic, suggesting that PHACE may have a complex pathogenesis. We report here genomic copy number variation (CNV) analysis of 98 individuals with PHACE syndrome as a first step in deciphering a potential genetic basis of PHACE syndrome. A total of 3,772 CNVs (2,507 duplications and 1,265 deletions) were detected in 98 individuals with PHACE syndrome. CNVs were then eliminated if they failed to meet established criteria for quality, spanned centromeres, or did not contain genes. CNVs were defined as "rare" if not documented in the database of genomic variants. Ten rare CNVs were discovered (size range: 134-406  kb), located at 1q32.1, 1q43, 3q26.32-3q26.33, 3p11.1, 7q33, 10q24.32, 12q24.13, 17q11.2, 18p11.31, and Xq28. There were no rare CNV events that occurred in more than one subject. Therefore, further study is needed to determine the significance of these CNVs in the pathogenesis of PHACE syndrome.
authors.affiliation: Departments of Dermatology and Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. Electronic address: dsiegel@mcw.edu.
authors.forename: Dawn H
authors.initials: DH
authors.lastname: Siegel
authors.affiliation: Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Joseph T C
authors.initials: JTC
authors.lastname: Shieh
authors.affiliation: Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kwon
authors.affiliation: Department of Dermatology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
authors.forename: Eulalia
authors.initials: E
authors.lastname: Baselga
authors.affiliation: Department of Hematology and Oncology, Vascular Birthmark Institute of New York, New York, New York, USA.
authors.forename: Francine
authors.initials: F
authors.lastname: Blei
authors.affiliation: Department of Dermatology, Hospital de Pediatria JP Garrahan, Buenos Aires, Argentina.
authors.forename: Maria
authors.initials: M
authors.lastname: Cordisco
authors.affiliation: Departments of Pediatrics and Neurology, University of Washington, Seattle, Washington, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.affiliation: Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Duffy
authors.affiliation: Departments of Dermatology and Pediatrics, Columbia University, Columbia, New York, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Garzon
authors.affiliation: Department of Bioinformatics and Computational Biology, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Gibbs
authors.affiliation: Departments of Surgery and Otolaryngology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Grimmer
authors.affiliation: Departments of Molecular and Medical Genetics, Pediatrics, and Neurology, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Hayflick
authors.affiliation: Departments of Dermatology and Pediatrics, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Alfons L
authors.initials: AL
authors.lastname: Krol
authors.affiliation: Department of Cardiovascular Research, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.affiliation: Department of Human and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Lorier
authors.affiliation: Department of Human and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Matter
authors.affiliation: Department of Biostatistics, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: McWeeney
authors.affiliation: Department of Dermatology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Metry
authors.affiliation: ARUP Clinical & Experimental Pathology, ARUP Laboratories, Salt Lake City, Utah, USA.
authors.forename: Sheri
authors.initials: S
authors.lastname: Mitchell
authors.affiliation: Departments of Pediatrics and Dermatology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Elena
authors.initials: E
authors.lastname: Pope
authors.affiliation: Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Santoro
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Stevenson
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Pinar
authors.initials: P
authors.lastname: Bayrak-Toydemir
authors.affiliation: Department of Biostatistics, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Wilmot
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Worthey
authors.affiliation: Departments of Dermatology and Pediatrics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Ilona J
authors.initials: IJ
authors.lastname: Frieden
authors.affiliation: Departments of Dermatology and Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Drolet
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Broeckel
mesh_terms: D000293:Adolescent; D000328:Adult; D001017:Aortic Coarctation / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D007223:Infant; D008297:Male; D020752:Neurocutaneous Syndromes / Q000235:genetics*; D015203:Reproducibility of Results; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D004247:DNA