Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region

Justine Coppinger, Donna McDonald-Mcginn, Elaine Zackai, Kate Shane, Joan F. Atkin, Alexander Asamoah, Robert Leland, David Weaver, Susan Lansky-Shafer, Karen Schmidt, Heidi Feldman, William Cohen, Judy Phalin, Berkley Powell, Blake C. Ballif, Aaron Theisen, Elizabeth Geiger, Chad Haldeman-Englert, Tamim H. Shaikh, Sulagna SaittaBassem A. Bejjani, Lisa G. Shaffer

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies. Because these deletions are mediated by low-copy repeats (LCRs), located distal to the 22q11.21 DiGeorge/velocardiofacial microdeletion region, duplications are predicted to occur with a frequency equal to the deletion. However, few microduplications of this region have been reported. We report the identification of 18 individuals with microduplications of 22q11.21-q11.23. The duplication boundaries for all individuals are within LCRs distal to the DiGeorge/velocardiofacial microdeletion region. Clinical records for nine subjects reveal shared characteristics, but also several examples of contradicting clinical features (e.g. macrocephaly versus microcephaly and upslanting versus downslanting palpebral fissures). Of 12 cases for whom parental DNA samples were available for testing, one is de novo and 11 inherited the microduplication from a parent, three of whom reportedly have learning problems or developmental delay. The variable phenotypes and preponderance of familial cases obfuscate the clinical relevance of the molecular data and emphasize the need for careful parental assessments and clinical correlations.

Original languageEnglish
Pages (from-to)1377-1383
Number of pages7
JournalHuman Molecular Genetics
Volume18
Issue number8
DOIs
StatePublished - 2009

Fingerprint

Genomic Segmental Duplications
Megalencephaly
Microcephaly
Eyelids
Intellectual Disability
Learning
Phenotype
DNA

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Coppinger, J., McDonald-Mcginn, D., Zackai, E., Shane, K., Atkin, J. F., Asamoah, A., ... Shaffer, L. G. (2009). Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region. Human Molecular Genetics, 18(8), 1377-1383. https://doi.org/10.1093/hmg/ddp042

Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region. / Coppinger, Justine; McDonald-Mcginn, Donna; Zackai, Elaine; Shane, Kate; Atkin, Joan F.; Asamoah, Alexander; Leland, Robert; Weaver, David; Lansky-Shafer, Susan; Schmidt, Karen; Feldman, Heidi; Cohen, William; Phalin, Judy; Powell, Berkley; Ballif, Blake C.; Theisen, Aaron; Geiger, Elizabeth; Haldeman-Englert, Chad; Shaikh, Tamim H.; Saitta, Sulagna; Bejjani, Bassem A.; Shaffer, Lisa G.

In: Human Molecular Genetics, Vol. 18, No. 8, 2009, p. 1377-1383.

Research output: Contribution to journalArticle

Coppinger, J, McDonald-Mcginn, D, Zackai, E, Shane, K, Atkin, JF, Asamoah, A, Leland, R, Weaver, D, Lansky-Shafer, S, Schmidt, K, Feldman, H, Cohen, W, Phalin, J, Powell, B, Ballif, BC, Theisen, A, Geiger, E, Haldeman-Englert, C, Shaikh, TH, Saitta, S, Bejjani, BA & Shaffer, LG 2009, 'Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region', Human Molecular Genetics, vol. 18, no. 8, pp. 1377-1383. https://doi.org/10.1093/hmg/ddp042
Coppinger, Justine ; McDonald-Mcginn, Donna ; Zackai, Elaine ; Shane, Kate ; Atkin, Joan F. ; Asamoah, Alexander ; Leland, Robert ; Weaver, David ; Lansky-Shafer, Susan ; Schmidt, Karen ; Feldman, Heidi ; Cohen, William ; Phalin, Judy ; Powell, Berkley ; Ballif, Blake C. ; Theisen, Aaron ; Geiger, Elizabeth ; Haldeman-Englert, Chad ; Shaikh, Tamim H. ; Saitta, Sulagna ; Bejjani, Bassem A. ; Shaffer, Lisa G. / Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 8. pp. 1377-1383.
@article{fcd62c5add964ec4bf1796543a314663,
title = "Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region",
abstract = "Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies. Because these deletions are mediated by low-copy repeats (LCRs), located distal to the 22q11.21 DiGeorge/velocardiofacial microdeletion region, duplications are predicted to occur with a frequency equal to the deletion. However, few microduplications of this region have been reported. We report the identification of 18 individuals with microduplications of 22q11.21-q11.23. The duplication boundaries for all individuals are within LCRs distal to the DiGeorge/velocardiofacial microdeletion region. Clinical records for nine subjects reveal shared characteristics, but also several examples of contradicting clinical features (e.g. macrocephaly versus microcephaly and upslanting versus downslanting palpebral fissures). Of 12 cases for whom parental DNA samples were available for testing, one is de novo and 11 inherited the microduplication from a parent, three of whom reportedly have learning problems or developmental delay. The variable phenotypes and preponderance of familial cases obfuscate the clinical relevance of the molecular data and emphasize the need for careful parental assessments and clinical correlations.",
author = "Justine Coppinger and Donna McDonald-Mcginn and Elaine Zackai and Kate Shane and Atkin, {Joan F.} and Alexander Asamoah and Robert Leland and David Weaver and Susan Lansky-Shafer and Karen Schmidt and Heidi Feldman and William Cohen and Judy Phalin and Berkley Powell and Ballif, {Blake C.} and Aaron Theisen and Elizabeth Geiger and Chad Haldeman-Englert and Shaikh, {Tamim H.} and Sulagna Saitta and Bejjani, {Bassem A.} and Shaffer, {Lisa G.}",
year = "2009",
doi = "10.1093/hmg/ddp042",
language = "English",
volume = "18",
pages = "1377--1383",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region

AU - Coppinger, Justine

AU - McDonald-Mcginn, Donna

AU - Zackai, Elaine

AU - Shane, Kate

AU - Atkin, Joan F.

AU - Asamoah, Alexander

AU - Leland, Robert

AU - Weaver, David

AU - Lansky-Shafer, Susan

AU - Schmidt, Karen

AU - Feldman, Heidi

AU - Cohen, William

AU - Phalin, Judy

AU - Powell, Berkley

AU - Ballif, Blake C.

AU - Theisen, Aaron

AU - Geiger, Elizabeth

AU - Haldeman-Englert, Chad

AU - Shaikh, Tamim H.

AU - Saitta, Sulagna

AU - Bejjani, Bassem A.

AU - Shaffer, Lisa G.

PY - 2009

Y1 - 2009

N2 - Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies. Because these deletions are mediated by low-copy repeats (LCRs), located distal to the 22q11.21 DiGeorge/velocardiofacial microdeletion region, duplications are predicted to occur with a frequency equal to the deletion. However, few microduplications of this region have been reported. We report the identification of 18 individuals with microduplications of 22q11.21-q11.23. The duplication boundaries for all individuals are within LCRs distal to the DiGeorge/velocardiofacial microdeletion region. Clinical records for nine subjects reveal shared characteristics, but also several examples of contradicting clinical features (e.g. macrocephaly versus microcephaly and upslanting versus downslanting palpebral fissures). Of 12 cases for whom parental DNA samples were available for testing, one is de novo and 11 inherited the microduplication from a parent, three of whom reportedly have learning problems or developmental delay. The variable phenotypes and preponderance of familial cases obfuscate the clinical relevance of the molecular data and emphasize the need for careful parental assessments and clinical correlations.

AB - Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies. Because these deletions are mediated by low-copy repeats (LCRs), located distal to the 22q11.21 DiGeorge/velocardiofacial microdeletion region, duplications are predicted to occur with a frequency equal to the deletion. However, few microduplications of this region have been reported. We report the identification of 18 individuals with microduplications of 22q11.21-q11.23. The duplication boundaries for all individuals are within LCRs distal to the DiGeorge/velocardiofacial microdeletion region. Clinical records for nine subjects reveal shared characteristics, but also several examples of contradicting clinical features (e.g. macrocephaly versus microcephaly and upslanting versus downslanting palpebral fissures). Of 12 cases for whom parental DNA samples were available for testing, one is de novo and 11 inherited the microduplication from a parent, three of whom reportedly have learning problems or developmental delay. The variable phenotypes and preponderance of familial cases obfuscate the clinical relevance of the molecular data and emphasize the need for careful parental assessments and clinical correlations.

UR - http://www.scopus.com/inward/record.url?scp=64549106899&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=64549106899&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddp042

DO - 10.1093/hmg/ddp042

M3 - Article

C2 - 19193630

AN - SCOPUS:64549106899

VL - 18

SP - 1377

EP - 1383

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 8

ER -