Abstract:
:Autism is a neurodevelopmental disorder of complex etiology in which genetic factors play a major role. We have implicated the neurexin 1 (NRXN1) gene in two independent subjects who display an autism spectrum disorder (ASD) in association with a balanced chromosomal abnormality involving 2p16.3. In the first, with karyotype 46,XX,ins(16;2)(q22.1;p16.1p16.3)pat, NRXN1 is directly disrupted within intron 5. Importantly, the father possesses the same chromosomal abnormality in the absence of ASD, indicating that the interruption of alpha-NRXN1 is not fully penetrant and must interact with other factors to produce ASD. The breakpoint in the second subject, with 46,XY,t(1;2)(q31.3;p16.3)dn, occurs approximately 750 kb 5' to NRXN1 within a 2.6 Mb genomic segment that harbors no currently annotated genes. A scan of the NRXN1 coding sequence in a cohort of ASD subjects, relative to non-ASD controls, revealed that amino acid alterations in neurexin 1 are not present at high frequency in ASD. However, a number of rare sequence variants in the coding region, including two missense changes in conserved residues of the alpha-neurexin 1 leader sequence and of an epidermal growth factor (EGF)-like domain, respectively, suggest that even subtle changes in NRXN1 might contribute to susceptibility to ASD.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Kim HG,Kishikawa S,Higgins AW,Seong IS,Donovan DJ,Shen Y,Lally E,Weiss LA,Najm J,Kutsche K,Descartes M,Holt L,Braddock S,Troxell R,Kaplan L,Volkmar F,Klin A,Tsatsanis K,Harris DJ,Noens I,Pauls DL,Daly MJ,MacDodoi
10.1016/j.ajhg.2007.09.011subject
Has Abstractpub_date
2008-01-01 00:00:00pages
199-207issue
1eissn
0002-9297issn
1537-6605pii
S0002-9297(07)00017-1journal_volume
82pub_type
杂志文章abstract::The affected sib-pair method has been used to investigate the mode of inheritance, and to estimate the "disease" allele frequency, for a number of HLA-associated diseases. One of the assumptions of the original sib-pair method is that the disease confers no selective disadvantage on affected individuals. This is obvio...
journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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