Genetic insights into childhood-onset schizophrenia: The yield of clinical exome sequencing

Anna Alkelai*, Lior Greenbaum, Shahar Shohat, Gundula Povysil, Ayan Malakar, Zhong Ren, Joshua E. Motelow, Tanya Schechter, Benjamin Draiman, Eti Chitrit-Raveh, Daniel Hughes, Vaidehi Jobanputra, Sagiv Shifman, David B. Goldstein, Yoav Kohn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Childhood-onset schizophrenia (COS) is a rare form of schizophrenia with an onset prior to 13 years of age. Although genetic factors play a role in COS etiology, only a few causal variants have been reported to date. This study presents a diagnostic exome sequencing (ES) in 37 Israeli Jewish families with a proband diagnosed with COS. By implementing a trio/duo ES approach and applying a well-established diagnostic pipeline, we detected clinically significant variants in 7 probands (19 %). These single nucleotide variants and indels were mostly inherited. The implicated genes were ANKRD11, GRIA2, CHD2, CLCN3, CLTC, IGF1R and MICU1. In a secondary analysis that compared COS patients to 4721 healthy controls, we observed that patients had a significant enrichment of rare loss of function (LoF) variants in LoF intolerant genes associated with developmental diseases. Taken together, ES could be considered as a valuable tool in the genetic workup for COS patients.

Original languageAmerican English
Pages (from-to)138-145
Number of pages8
JournalSchizophrenia Research
StatePublished - Feb 2023

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© 2023 Elsevier B.V.


  • Childhood onset schizophrenia
  • Diagnostic yield
  • Whole exome sequencing


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