Copy number variation analysis in 98 individuals with PHACE syndrome

Dawn H. Siegel; Joseph T.C. Shieh; Eun Kyung Kwon; Eulalia Baselga; Francine Blei; Maria Cordisco; William B. Dobyns; Kelly J. Duffy; Maria C. Garzon; David L. Gibbs; Johannes F. Grimmer; Susan J. Hayflick; Alfons L. Krol; Pui Yan Kwok; Rachel Lorier; Andrea Matter; Shannon McWeeney; Denise Metry; Sheri Mitchell; Elena Pope; Jennifer L. Santoro; David A. Stevenson; Pinar Bayrak-Toydemir; Beth Wilmot; Elizabeth A. Worthey; Ilona J. Frieden; Beth A. Drolet; Ulrich Broeckel

doi:10.1038/jid.2012.367

Copy number variation analysis in 98 individuals with PHACE syndrome

Dawn H. Siegel, Joseph T.C. Shieh, Eun Kyung Kwon, Eulalia Baselga, Francine Blei, Maria Cordisco, William B. Dobyns, Kelly J. Duffy, Maria C. Garzon, David L. Gibbs, Johannes F. Grimmer, Susan J. Hayflick, Alfons L. Krol, Pui Yan Kwok, Rachel Lorier, Andrea Matter, Shannon McWeeney, Denise Metry, Sheri Mitchell, Elena PopeJennifer L. Santoro, David A. Stevenson, Pinar Bayrak-Toydemir, Beth Wilmot, Elizabeth A. Worthey, Ilona J. Frieden, Beth A. Drolet, Ulrich Broeckel

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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.

Original language	English (US)
Pages (from-to)	677-684
Number of pages	8
Journal	Journal of Investigative Dermatology
Volume	133
Issue number	3
DOIs	https://doi.org/10.1038/jid.2012.367
State	Published - Mar 2013
Externally published	Yes

Bibliographical note

Funding Information:
We thank Shawna Joachim for assisting with study coordination and manuscript preparation and Gina Im for assisting with data management. We are grateful to the families for their participation in the study and to the physicians who referred patients for this study. This publication was made possible with support from the Oregon Clinical and Translational Research Institute, by grant# UL1 RR024140 from the National Center for Research Resources (NCRR), and by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). Additional funding sources include Society for Pediatric Dermatology (DHS), Dermatology Foundation (DHS), Greater Milwaukee Foundation (DHS, BD), Families, Society of Pediatric Otolaryngology, Public Health Services research grants UL1-RR025764 and C06-RR11234 from the NCRR, the Children’s Health Research Center and Clinical Genetics Research Program at the University of Utah, and the American Society of Pediatric Otolaryngology (JFG, PBT, SM, DHS). JS was funded by NIH/NHLBI K08HL092970. The project was supported in part by funds from Children’s Research Institute, Medical College of Wisconsin (UB).

Access

10.1038/jid.2012.367

OpenUrl availability

Full text

Cite this

Siegel, D. H., Shieh, J. T. C., Kwon, E. K., Baselga, E., Blei, F., Cordisco, M., Dobyns, W. B., Duffy, K. J., Garzon, M. C., Gibbs, D. L., Grimmer, J. F., Hayflick, S. J., Krol, A. L., Kwok, P. Y., Lorier, R., Matter, A., McWeeney, S., Metry, D., Mitchell, S., ... Broeckel, U. (2013). Copy number variation analysis in 98 individuals with PHACE syndrome. Journal of Investigative Dermatology, 133(3), 677-684. https://doi.org/10.1038/jid.2012.367

Siegel, DH, Shieh, JTC, Kwon, EK, Baselga, E, Blei, F, Cordisco, M, Dobyns, WB, Duffy, KJ, Garzon, MC, Gibbs, DL, Grimmer, JF, Hayflick, SJ, Krol, AL, Kwok, PY, Lorier, R, Matter, A, McWeeney, S, Metry, D, Mitchell, S, Pope, E, Santoro, JL, Stevenson, DA, Bayrak-Toydemir, P, Wilmot, B, Worthey, EA, Frieden, IJ, Drolet, BA & Broeckel, U 2013, 'Copy number variation analysis in 98 individuals with PHACE syndrome', Journal of Investigative Dermatology, vol. 133, no. 3, pp. 677-684. https://doi.org/10.1038/jid.2012.367

@article{610bc6673864471d8ba9bef78d54919b,

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.",

author = "Siegel, {Dawn H.} and Shieh, {Joseph T.C.} and Kwon, {Eun Kyung} and Eulalia Baselga and Francine Blei and Maria Cordisco and Dobyns, {William B.} and Duffy, {Kelly J.} and Garzon, {Maria C.} and Gibbs, {David L.} and Grimmer, {Johannes F.} and Hayflick, {Susan J.} and Krol, {Alfons L.} and Kwok, {Pui Yan} and Rachel Lorier and Andrea Matter and Shannon McWeeney and Denise Metry and Sheri Mitchell and Elena Pope and Santoro, {Jennifer L.} and Stevenson, {David A.} and Pinar Bayrak-Toydemir and Beth Wilmot and Worthey, {Elizabeth A.} and Frieden, {Ilona J.} and Drolet, {Beth A.} and Ulrich Broeckel",

note = "Funding Information: We thank Shawna Joachim for assisting with study coordination and manuscript preparation and Gina Im for assisting with data management. We are grateful to the families for their participation in the study and to the physicians who referred patients for this study. This publication was made possible with support from the Oregon Clinical and Translational Research Institute, by grant# UL1 RR024140 from the National Center for Research Resources (NCRR), and by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). Additional funding sources include Society for Pediatric Dermatology (DHS), Dermatology Foundation (DHS), Greater Milwaukee Foundation (DHS, BD), Families, Society of Pediatric Otolaryngology, Public Health Services research grants UL1-RR025764 and C06-RR11234 from the NCRR, the Children{\textquoteright}s Health Research Center and Clinical Genetics Research Program at the University of Utah, and the American Society of Pediatric Otolaryngology (JFG, PBT, SM, DHS). JS was funded by NIH/NHLBI K08HL092970. The project was supported in part by funds from Children{\textquoteright}s Research Institute, Medical College of Wisconsin (UB). ",

year = "2013",

month = mar,

doi = "10.1038/jid.2012.367",

language = "English (US)",

volume = "133",

pages = "677--684",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "Nature Publishing Group",

number = "3",

}

TY - JOUR

T1 - Copy number variation analysis in 98 individuals with PHACE syndrome

AU - Siegel, Dawn H.

AU - Shieh, Joseph T.C.

AU - Kwon, Eun Kyung

AU - Baselga, Eulalia

AU - Blei, Francine

AU - Cordisco, Maria

AU - Dobyns, William B.

AU - Duffy, Kelly J.

AU - Garzon, Maria C.

AU - Gibbs, David L.

AU - Grimmer, Johannes F.

AU - Hayflick, Susan J.

AU - Krol, Alfons L.

AU - Kwok, Pui Yan

AU - Lorier, Rachel

AU - Matter, Andrea

AU - McWeeney, Shannon

AU - Metry, Denise

AU - Mitchell, Sheri

AU - Pope, Elena

AU - Santoro, Jennifer L.

AU - Stevenson, David A.

AU - Bayrak-Toydemir, Pinar

AU - Wilmot, Beth

AU - Worthey, Elizabeth A.

AU - Frieden, Ilona J.

AU - Drolet, Beth A.

AU - Broeckel, Ulrich

N1 - Funding Information: We thank Shawna Joachim for assisting with study coordination and manuscript preparation and Gina Im for assisting with data management. We are grateful to the families for their participation in the study and to the physicians who referred patients for this study. This publication was made possible with support from the Oregon Clinical and Translational Research Institute, by grant# UL1 RR024140 from the National Center for Research Resources (NCRR), and by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). Additional funding sources include Society for Pediatric Dermatology (DHS), Dermatology Foundation (DHS), Greater Milwaukee Foundation (DHS, BD), Families, Society of Pediatric Otolaryngology, Public Health Services research grants UL1-RR025764 and C06-RR11234 from the NCRR, the Children’s Health Research Center and Clinical Genetics Research Program at the University of Utah, and the American Society of Pediatric Otolaryngology (JFG, PBT, SM, DHS). JS was funded by NIH/NHLBI K08HL092970. The project was supported in part by funds from Children’s Research Institute, Medical College of Wisconsin (UB).

PY - 2013/3

Y1 - 2013/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84873703270&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873703270&partnerID=8YFLogxK

U2 - 10.1038/jid.2012.367

DO - 10.1038/jid.2012.367

M3 - Article

C2 - 23096700

AN - SCOPUS:84873703270

SN - 0022-202X

VL - 133

SP - 677

EP - 684

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 3

ER -

Copy number variation analysis in 98 individuals with PHACE syndrome

Abstract

Bibliographical note

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this