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

被引：60

作者：

Coppinger, Justine ^{[1
]}

McDonald-McGinn, Donna ^{[2
]}

Zackai, Elaine ^{[2
]}

Shane, Kate ^{[3
]}

Atkin, Joan F. ^{[3
]}

Asamoah, Alexander ^{[4
]}

Leland, Robert ^{[5
]}

Weaver, David D. ^{[6
]}

Lansky-Shafer, Susan ^{[7
]}

Schmidt, Karen ^{[8
]}

Feldman, Heidi ^{[8
]}

Cohen, William ^{[8
]}

Phalin, Judy ^{[9
]}

Powell, Berkley ^{[9
]}

Ballif, Blake C. ^{[1
]}

Theisen, Aaron ^{[1
]}

Geiger, Elizabeth ^{[2
]}

Haldeman-Englert, Chad ^{[2
]}

Shaikh, Tamim H. ^{[2
]}

Saitta, Sulagna ^{[2
]}

Bejjani, Bassem A. ^{[1
,10
,11
]}

Shaffer, Lisa G. ^{[1
,12
]}

机构：

[1] Signature Genom Labs LLC, Spokane, WA 99207 USA

[2] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA

[3] Ohio State Univ, Dept Pediat, Nationwide Childrens Hosp, Columbus, OH 43210 USA

[4] Univ Louisville, Weisskopf Child Evaluat Ctr, Louisville, KY 40292 USA

[5] Cheyenne Childrens Clin, Cheyenne, WY USA

[6] Indiana Univ, Sch Med, Dept Mol & Human Genet, Indianapolis, IN USA

[7] Carle Clin Assoc, Dept Med Genet, Bloomington, IL USA

[8] Childrens Hosp Pittsburgh, Dept Med Genet, Pittsburgh, PA 15213 USA

[9] Childrens Hosp Cent Calif, Madera, CA USA

[10] Sacred Heart Med Ctr, Spokane, WA USA

[11] Washington State Univ, WWAMI Med Educ Program, Spokane, WA USA

[12] Washington State Univ, Sch Mol Biosci, Spokane, WA USA

来源：

HUMAN MOLECULAR GENETICS | 2009年 / 18卷 / 08期

基金：

美国国家卫生研究院;

关键词：

LOW COPY REPEATS; CHROMOSOMAL REARRANGEMENTS; DELETION SYNDROME; CONGENITAL-ANOMALIES; DUPLICATION SYNDROME; COGNITIVE DEFICITS; DIGEORGE-SYNDROME; INDIVIDUALS; MECHANISMS; RECOMBINATION;

D O I：

10.1093/hmg/ddp042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1377 / 1383

页数：7

共 32 条

[1] 1.5 Mb de novo 22q11.21 microduplication in a patient with cognitive deficits and dysmorphic facial features [J].