|
|
| PMID |
|
|
| TITLE |
|
| Association between microdeletion and microduplication at 16p11.2 and autism. |
|
| ABSTRACT |
|
| BACKGROUND |
NlmCategory: BACKGROUND |
| Autism spectrum disorder is a heritable developmental disorder in which chromosomal abnormalities are thought to play a role. |
| METHODS |
NlmCategory: METHODS |
| As a first component of a genomewide association study of families from the Autism Genetic Resource Exchange (AGRE), we used two novel algorithms to search for recurrent copy-number variations in genotype data from 751 multiplex families with autism. Specific recurrent de novo events were further evaluated in clinical-testing data from Children's Hospital Boston and in a large population study in Iceland. |
| RESULTS |
NlmCategory: RESULTS |
| Among the AGRE families, we observed five instances of a de novo deletion of 593 kb on chromosome 16p11.2. Using comparative genomic hybridization, we observed the identical deletion in 5 of 512 children referred to Children's Hospital Boston for developmental delay, mental retardation, or suspected autism spectrum disorder, as well as in 3 of 299 persons with autism in an Icelandic population; the deletion was also carried by 2 of 18,834 unscreened Icelandic control subjects. The reciprocal duplication of this region occurred in 7 affected persons in AGRE families and 4 of the 512 children from Children's Hospital Boston. The duplication also appeared to be a high-penetrance risk factor. |
| CONCLUSIONS |
NlmCategory: CONCLUSIONS |
| We have identified a novel, recurrent microdeletion and a reciprocal microduplication that carry substantial susceptibility to autism and appear to account for approximately 1% of cases. We did not identify other regions with similar aggregations of large de novo mutations. |
| Copyright 2008 Massachusetts Medical Society. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| aheadofprint |
2008/01/09 |
| pubmed |
2008/01/11 09:00 |
| medline |
2008/02/20 09:00 |
| entrez |
2008/01/11 09:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Weiss LA |
|
Weiss |
Lauren A |
LA |
|
Autism Consortium , Boston, USA. |
| Shen Y |
|
Shen |
Yiping |
Y |
|
|
| Korn JM |
|
Korn |
Joshua M |
JM |
|
|
| Arking DE |
|
Arking |
Dan E |
DE |
|
|
| Miller DT |
|
Miller |
David T |
DT |
|
|
| Fossdal R |
|
Fossdal |
Ragnheidur |
R |
|
|
| Saemundsen E |
|
Saemundsen |
Evald |
E |
|
|
| Stefansson H |
|
Stefansson |
Hreinn |
H |
|
|
| Ferreira MA |
|
Ferreira |
Manuel A R |
MA |
|
|
| Green T |
|
Green |
Todd |
T |
|
|
| Platt OS |
|
Platt |
Orah S |
OS |
|
|
| Ruderfer DM |
|
Ruderfer |
Douglas M |
DM |
|
|
| Walsh CA |
|
Walsh |
Christopher A |
CA |
|
|
| Altshuler D |
|
Altshuler |
David |
D |
|
|
| Chakravarti A |
|
Chakravarti |
Aravinda |
A |
|
|
| Tanzi RE |
|
Tanzi |
Rudolph E |
RE |
|
|
| Stefansson K |
|
Stefansson |
Kari |
K |
|
|
| Santangelo SL |
|
Santangelo |
Susan L |
SL |
|
|
| Gusella JF |
|
Gusella |
James F |
JF |
|
|
| Sklar P |
|
Sklar |
Pamela |
P |
|
|
| Wu BL |
|
Wu |
Bai-Lin |
BL |
|
|
| Daly MJ |
|
Daly |
Mark J |
MJ |
|
|
|
Autism Consortium |
|
|
|
|
|
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 358 |
| ISSUE: 7 |
| TITLE: The New England journal of medicine |
| ISOABBREVIATION: N. Engl. J. Med. |
| YEAR: 2008 |
| MONTH: Feb |
| DAY: 14 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1533-4406 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: N Engl J Med |
| COUNTRY: United States |
| ISSNLINKING: 0028-4793 |
| NLMUNIQUEID: 0255562 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| CommentIn |
N Engl J Med. 2008 Feb 14;358(7):737-9 |
18184953 |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| R01-MN071425-01A1 |
OMHHE CDC HHS |
United States |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Autistic Disorder |
genetics |
| Child |
genetics |
| Chromosome Aberrations |
genetics |
| Chromosome Deletion |
genetics |
| Chromosomes, Human, Pair 15 |
genetics |
| Chromosomes, Human, Pair 16 |
genetics |
| DNA Mutational Analysis |
genetics |
| Developmental Disabilities |
genetics |
| Female |
genetics |
| Genetic Predisposition to Disease |
genetics |
| Genotype |
genetics |
| Humans |
genetics |
| Intellectual Disability |
genetics |
| Male |
genetics |
| Phenotype |
genetics |
| Sequence Analysis, DNA |
methods |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
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| CHEMICALS |
|
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| OTHER ID's |
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