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 language | English |
|---|---|
| Pages (from-to) | 1377-1383 |
| Number of pages | 7 |
| Journal | Human Molecular Genetics |
| Volume | 18 |
| Issue number | 8 |
| DOIs | |
| State | Published - 2009 |
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ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
- Molecular Biology
Cite this
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 journal › Article
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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.
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U2 - 10.1093/hmg/ddp042
DO - 10.1093/hmg/ddp042
M3 - Article
VL - 18
SP - 1377
EP - 1383
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 8
ER -