Abstract:
BACKGROUND:Copy number variants in coding and noncoding genomic regions have been implicated as risk factor for schizophrenia (SCZ). Rare duplications of the RB1CC1 gene were found enriched in SCZ patients. Considering that the effect of such duplications on RB1CC1 expression has never been evaluated and partial gene duplications of RB1CC1 have also been reported in SCZ patients, it is unclear whether the pathogenesis is mediated by haploinsufficiency rather than genuine overexpression of the gene. METHODS AND RESULTS:We studied a patient with schizophrenia, suicidality, and obesity, who carried a de novo RB1CC1 complete duplication, as assessed by high-resolution array-CGH. Molecular breakpoint cloning allowed to identify nonhomologous end joining (NHEJ) as driving mechanism in this rearrangement. On the contrary, trio-based whole-exome sequencing excluded other potential causative variants related to the phenotype. Functional assays showed significant overexpression of RB1CC1 in the peripheral blood lymphocytes of the proband compared to control subjects, suggesting overdosage as leading mechanism in SCZ pathophysiology. CONCLUSION:We hypothesized a pathogenetic model that might explain the correlation between RB1CC1 overexpression and schizophrenia by altering different cell signaling pathways, including autophagy, a promising therapeutic target for schizophrenic patients.
journal_name
Mol Genet Genomic Medjournal_title
Molecular genetics & genomic medicineauthors
Errichiello E,Giorda R,Gambale A,Iolascon A,Zuffardi O,Giglio Sdoi
10.1002/mgg3.1561subject
Has Abstractpub_date
2020-12-19 00:00:00pages
e1561issn
2324-9269pub_type
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2019-07-01 00:00:00
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更新日期:2019-02-01 00:00:00
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更新日期:2020-10-01 00:00:00
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更新日期:2019-07-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1424
更新日期:2020-10-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.227
更新日期:2016-06-07 00:00:00
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pub_type: 杂志文章
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更新日期:2017-07-28 00:00:00
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journal_title:Molecular genetics & genomic medicine
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2020-09-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2018-05-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
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更新日期:2020-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2014-11-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2013-11-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章,评审
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更新日期:2018-11-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2019-06-01 00:00:00