2011 Fiscal Year Final Research Report
Delineation of molecular basis of autism using array CGH
| Project/Area Number |
21591341
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | National Research Institute for Child Health and Development |
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Principal Investigator |
KOSAKI Rika 独立行政法人国立成育医療研究センター, 器官病態系内科部・遺伝診療科, 医長 (50234745)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 小児神経学 / オリゴDNAアレイ / CGH法 / 自閉症 / 遺伝 / アレイCGH |
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| Research Abstract |
Autism is a complex developmental disability that typically appears during the first three years of life and is the result of a neurological disorder that affects the normal functioning of the brain, impacting development in the areas of social interaction and communication skills. Presumably, genetic background contributes to autism. Yet, only 10% of patients exhibit definitive genetic abnormalities. We designed a custom array with 60000 probes. Probes were densely allocated at genes on X chromosome, genes of which mutations are known to cause multiple malformation syndromes with developmental delay(i. e. Cornelia de Lange syndrome, Rubinstein-Taybi syndrome), and genes already known to be related with autism(NLGN3, NGLN4, NRXN1, SHANK3, CNTNAP2, PCDH10, CNTN3, NHE9, NHE6, DIA1, and A2BP1) and their homologous/upstream/downstream genes.
We have identified two critical cases : One patient who had a duplication of 5.4MB at 6q14, 2-15 including the GABA receptor GABRB3 ; the other patient had a deletion of 6.6MB at 2p16.3 including NRXN1. NRXN forms a complex with NLGN on the post synaptic membrane and plays a critical role on neural transmission mediated through GABA receptors and glutamine receptors. We suggest that duplication of GABRB3 and deletion of NRXN1 contributes to autism.
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[Journal Article] Clinical application of array-based comparative genomic hybridization by two-stage screening for 536 patients with mental retardation and multiple congenital anomalies2011
Author(s)
Hayashi S, Imoto I, Aizu Y, Okamoto N, Mizuno S, Kurosawa K, Okamoto N, Honda S, Araki S, Mizutani S, Numabe H, Saitoh S, Kosho T, Fukushima Y, Mitsubuchi H, Endo F, Chinen Y, Kosaki R, Okuyama T, Ohki H, Yoshihashi H, Ono M, Takada F, Ono H, Yagi M, Matsumoto H, Makita Y, Hata A, Inazawa J
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Journal Title
J Hum Genet
Volume: 56(2)
Pages: 110-24
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