Disruption of neurexin 1 associated with autism spectrum disorder. Export

@article{citeulike:6043618, 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.}, author = {Kim, Hyung-Goo G. and Kishikawa, Shotaro and Higgins, Anne W. and Seong, Ihn-Sik S. and Donovan, Diana J. and Shen, Yiping and Lally, Eric and Weiss, Lauren A. and Najm, Juliane and Kutsche, Kerstin and Descartes, Maria and Holt, Lynn and Braddock, Stephen and Troxell, Robin and Kaplan, Lee and Volkmar, Fred and Klin, Ami and Tsatsanis, Katherine and Harris, David J. and Noens, Ilse and Pauls, David L. and Daly, Mark J. and MacDonald, Marcy E. and Morton, Cynthia C. and Quade, Bradley J. and Gusella, James F.}, citeulike-article-id = {6043618}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.ajhg.2007.09.011}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18179900}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18179900}, doi = {10.1016/j.ajhg.2007.09.011}, issn = {1537-6605}, journal = {American journal of human genetics}, keywords = {autism, nrxn1}, month = {January}, number = {1}, pages = {199--207}, posted-at = {2009-10-30 16:34:48}, priority = {2}, title = {Disruption of neurexin 1 associated with autism spectrum disorder.}, url = {http://dx.doi.org/10.1016/j.ajhg.2007.09.011}, volume = {82}, year = {2008} }

TY - JOUR ID - citeulike:6043618 L3 - citeulike-article-id:6043618 N2 - 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. IS - 1 JF - American journal of human genetics SN - 1537-6605 EP - 207 TI - Disruption of neurexin 1 associated with autism spectrum disorder. VL - 82 SP - 199 KW - autism KW - nrxn1 AU - Kim, Hyung-Goo AU - Kishikawa, Shotaro AU - Higgins, Anne AU - Seong, Ihn-Sik AU - Donovan, Diana AU - Shen, Yiping AU - Lally, Eric AU - Weiss, Lauren AU - Najm, Juliane AU - Kutsche, Kerstin AU - Descartes, Maria AU - Holt, Lynn AU - Braddock, Stephen AU - Troxell, Robin AU - Kaplan, Lee AU - Volkmar, Fred AU - Klin, Ami AU - Tsatsanis, Katherine AU - Harris, David AU - Noens, Ilse AU - Pauls, David AU - Daly, Mark AU - MacDonald, Marcy AU - Morton, Cynthia AU - Quade, Bradley AU - Gusella, James PY - 2008/01// UR - http://dx.doi.org/10.1016/j.ajhg.2007.09.011 ER -