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

doi:10.1016/j.schres.2022.12.033

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

Tel Aviv University, The Hebrew University of Jerusalem

Research output: Contribution to journal › Article › peer-review

Abstract

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 language	English
Pages (from-to)	138-145
Number of pages	8
Journal	Schizophrenia Research
Volume	252
DOIs	https://doi.org/10.1016/j.schres.2022.12.033
State	Published - Feb 2023

Keywords

Childhood onset schizophrenia
Diagnostic yield
Whole exome sequencing

All Science Journal Classification (ASJC) codes

Psychiatry and Mental health
Biological Psychiatry

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10.1016/j.schres.2022.12.033

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Alkelai, A., Greenbaum, L., Shohat, S., Povysil, G., Malakar, A., Ren, Z., Motelow, J. E., Schechter, T., Draiman, B., Chitrit-Raveh, E., Hughes, D., Jobanputra, V., Shifman, S., Goldstein, D. B., & Kohn, Y. (2023). Genetic insights into childhood-onset schizophrenia: The yield of clinical exome sequencing. Schizophrenia Research, 252, 138-145. https://doi.org/10.1016/j.schres.2022.12.033

@article{49a0884e3ddb44739a5a1ebc233aa238,

title = "Genetic insights into childhood-onset schizophrenia: The yield of clinical exome sequencing",

abstract = "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.",

keywords = "Childhood onset schizophrenia, Diagnostic yield, Whole exome sequencing",

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

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier B.V.",

year = "2023",

month = feb,

doi = "10.1016/j.schres.2022.12.033",

language = "الإنجليزيّة",

volume = "252",

pages = "138--145",

journal = "Schizophrenia Research",

issn = "0920-9964",

publisher = "Elsevier",

}

Alkelai, A, Greenbaum, L, Shohat, S, Povysil, G, Malakar, A, Ren, Z, Motelow, JE, Schechter, T, Draiman, B, Chitrit-Raveh, E, Hughes, D, Jobanputra, V, Shifman, S, Goldstein, DB & Kohn, Y 2023, 'Genetic insights into childhood-onset schizophrenia: The yield of clinical exome sequencing', Schizophrenia Research, vol. 252, pp. 138-145. https://doi.org/10.1016/j.schres.2022.12.033

TY - JOUR

T1 - Genetic insights into childhood-onset schizophrenia

T2 - The yield of clinical exome sequencing

AU - Alkelai, Anna

AU - Greenbaum, Lior

AU - Shohat, Shahar

AU - Povysil, Gundula

AU - Malakar, Ayan

AU - Ren, Zhong

AU - Motelow, Joshua E.

AU - Schechter, Tanya

AU - Draiman, Benjamin

AU - Chitrit-Raveh, Eti

AU - Hughes, Daniel

AU - Jobanputra, Vaidehi

AU - Shifman, Sagiv

AU - Goldstein, David B.

AU - Kohn, Yoav

PY - 2023/2

Y1 - 2023/2

N2 - 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.

AB - 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.

KW - Childhood onset schizophrenia

KW - Diagnostic yield

KW - Whole exome sequencing

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U2 - 10.1016/j.schres.2022.12.033

DO - 10.1016/j.schres.2022.12.033

M3 - مقالة

C2 - 36645932

SN - 0920-9964

VL - 252

SP - 138

EP - 145

JO - Schizophrenia Research

JF - Schizophrenia Research

ER -

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

Abstract

Keywords

All Science Journal Classification (ASJC) codes

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