Dataset Information

Mutation screening of SCN2A in schizophrenia and identification of a novel loss-of-function mutation.

ABSTRACT:

Objectives

There is a growing body of evidence suggesting a shared genetic susceptibility between many neuropsychiatric disorders, including schizophrenia, autism, intellectual disability (ID) and epilepsy. The sodium channel, voltage-gated type II α subunit gene SCN2A has been shown to exhibit loss-of-function (LoF) mutations in individuals with seizure disorders, ID, autism and schizophrenia. The role of LoF mutations in schizophrenia is still uncertain with only one such mutation identified to date.

Methods

To seek additional evidence for a role for LoF mutations at SCN2A in schizophrenia we performed mutation screening of the entire coding sequence in 980 schizophrenia cases. Given an absence of LoF mutations in a public exome cohort (ESP6500, N=6503), we did not additionally sequence controls.

Results

We identified a novel, nonsense (i.e. stop codon) mutation in one case (E169X) that is absent in 4300 European-American and 2203 African-American individuals from the NHLBI Exome Sequencing Project. This is the second LoF allele identified in a schizophrenia case to date. We also show a novel, missense variant, V1282F, that occurs in two cases and is absent in the control dataset.

Conclusion

We argue that very rare, LoF mutations at SCN2A act in a moderately penetrant manner to increase the risk of developing several neuropsychiatric disorders including seizure disorders, ID, autism and schizophrenia.

SUBMITTER: Carroll LS

PROVIDER: S-EPMC4756433 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Publications

Mutation screening of SCN2A in schizophrenia and identification of a novel loss-of-function mutation.

Carroll Liam S LS Woolf Rebecca R Ibrahim Yousef Y Williams Hywel J HJ Dwyer Sarah S Walters James J Kirov George G O'Donovan Michael C MC Owen Michael J MJ

Psychiatric genetics 20160401 2

<h4>Objectives</h4>There is a growing body of evidence suggesting a shared genetic susceptibility between many neuropsychiatric disorders, including schizophrenia, autism, intellectual disability (ID) and epilepsy. The sodium channel, voltage-gated type II α subunit gene SCN2A has been shown to exhibit loss-of-function (LoF) mutations in individuals with seizure disorders, ID, autism and schizophrenia. The role of LoF mutations in schizophrenia is still uncertain with only one such mutation iden ...[more]

PMID: 26555645

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Dataset Information

Mutation screening of SCN2A in schizophrenia and identification of a novel loss-of-function mutation.

Objectives

Methods

Results

Conclusion

Publications

Mutation screening of SCN2A in schizophrenia and identification of a novel loss-of-function mutation.

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