Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders

被引：249

作者：

Miller, D. T. ^{[1
,2
,12
,13
]}

Shen, Y. ^{[1
,2
,3
,12
]}

Weiss, L. A. ^{[1
,2
,3
]}

Korn, J. ^{[4
]}

Anselm, I. ^{[1
,5
]}

Bridgemohan, C. ^{[1
,6
]}

Cox, G. F. ^{[1
,7
,13
]}

Dickinson, H. ^{[8
]}

Gentile, J. ^{[1
,9
,13
]}

Harris, D. J. ^{[1
,13
]}

Hegde, V. ^{[1
,13
]}

Hundley, R. ^{[1
,6
]}

Khwaja, O. ^{[1
,2
,5
]}

Kothare, S. ^{[1
,5
,10
]}

Luedke, C. ^{[1
,11
]}

Nasir, R. ^{[1
,2
,6
]}

Poduri, A. ^{[1
,5
]}

Prasad, K. ^{[1
,5
]}

Raffalli, P. ^{[1
,5
]}

Reinhard, A. ^{[12
,13
]}

Smith, S. E. ^{[1
,7
,13
]}

Sobeih, M. M. ^{[1
,2
,5
]}

Soul, J. S. ^{[1
,5
]}

Stoler, J. ^{[1
,13
]}

Takeoka, M. ^{[1
,5
,10
]}

Tan, W-H ^{[1
,13
]}

Thakuria, J. ^{[1
,13
]}

Wolff, R. ^{[1
,5
]}

Yusupov, R. ^{[1
,13
]}

Gusella, J. F. ^{[1
,2
,3
]}

Daly, M. J. ^{[1
,2
,3
,4
]}

Wu, B-L ^{[1
,2
,4
,12
]}

机构：

[1] Harvard Univ, Sch Med, Boston, MA USA

[2] Autism Consortium, Boston, MA USA

[3] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[4] Broad Inst Harvard & MIT, Cambridge, MA USA

[5] Childrens Hosp Boston, Dept Neurol, Boston, MA 02115 USA

[6] Childrens Hosp Boston, Div Dev Med, Boston, MA 02115 USA

[7] Genzyme Corp, Cambridge, MA USA

[8] Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, Boston, MA 02115 USA

[9] Childrens Hosp Boston, Dept Psychiat, Boston, MA 02115 USA

[10] Childrens Hosp Boston, Div Epilepsy & Clin Neurophysiol, Boston, MA 02115 USA

[11] Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA

[12] Childrens Hosp Boston, Dept Lab Med, Boston, MA 02115 USA

[13] Childrens Hosp Boston, Div Genet, Boston, MA 02115 USA

来源：

JOURNAL OF MEDICAL GENETICS | 2009年 / 46卷 / 04期

基金：

美国国家卫生研究院;

关键词：

COMPARATIVE GENOMIC HYBRIDIZATION; OBSESSIVE-COMPULSIVE DISORDER; JUVENILE MYOCLONIC EPILEPSY; (AC)N DINUCLEOTIDE REPEAT; RECEPTOR SUBUNIT GENE; PRADER-WILLI-SYNDROME; BIPOLAR DISORDER; LINKAGE DISEQUILIBRIUM; CHROMOSOME; 15Q13-14; PARTIAL DUPLICATION;

D O I：

10.1136/jmg.2008.059907

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background: Segmental duplications at breakpoints (BP4-BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or electroencephalogram (EEG) abnormalities. Patients: DNA samples from 1445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children's Hospital Boston and DNA samples from 1441 individuals with autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository. Results: We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4-BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4-BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, attention deficit hyperactivity disorder, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4-BP5 covers similar to 1.5 Mb (chr15: 28.719-30.298 Mb) and includes six reference genes and 1 miRNA gene, while the smaller duplications cover similar to 500 kb (chr15: 28.902-29.404 Mb) and contain three reference genes and one miRNA gene. The BP4-BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG. Conclusions: The phenotype of chromosome 15q13.2q13.3 BP4-BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying aetiology of this syndrome.

引用

页码：242 / 248

页数：7

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