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Annotation

Sun C, Cheng MC, Qin R, Liao DL, Chen TT, Koong FJ, Chen G, Chen CH. Identification and functional characterization of rare mutations of the neuroligin-2 gene (NLGN2) associated with schizophrenia. Hum Mol Genet . 2011 Aug 1 ; 20(15):3042-51. PubMed Abstract

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Comment by:  Anna Need
Submitted 25 May 2011 Posted 25 May 2011

Sun et al. sequenced a cohort of 584 schizophrenia patients and 549 controls to look for rare variants in the NLGN2 gene. They found several missense variants, but no significant excess in cases (8/584 vs. 2/549, p = 0.07). Polyphen predicted one (a case-only variant) to be probably damaging, and another to be possibly damaging, and the rest to be benign. Their own extensive functional work showed the “possibly damaging” one to have no obvious effect on function; rather, it was a loss-of-function mutation. The patient had no family history of mental illness, yet the mutation was shared by the one relative from whom they could obtain DNA—an unaffected brother—suggesting that it was inherited from one of the unaffected parents.

Overall, although the variant certainly seems to be functional, there isn’t really any good evidence that it is involved in schizophrenia in this patient. The gene is a good candidate, but there was no evidence for an excess of mutations in the schizophrenia patients versus the controls. The family history, the presence in the unaffected...  Read more


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