Identification of Rare Mutations of Two Presynaptic Cytomatrix Genes <i>BSN</i> and <i>PCLO</i> in Schizophrenia and Bipolar Disorder

Schizophrenia and bipolar disorder are severe mental disorders with a major component of genetic factors in their etiology. Rare mutations play a significant role in these two disorders, and they are highly heterogeneous and personalized. Identification of personalized mutations is essential for the...

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Autores principales:	Chia-Hsiang Chen, Yu-Shu Huang, Ding-Lieh Liao, Cheng-Yi Huang, Chia-Heng Lin, Ting-Hsuan Fang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	schizophrenia bipolar disorder presynaptic cytomatrix active zone neurotransmission Medicine R
Acceso en línea:	https://doaj.org/article/246103831b9e46b2a32a8d2e4c3474bc
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spelling	oai:doaj.org-article:246103831b9e46b2a32a8d2e4c3474bc2021-11-25T18:06:47ZIdentification of Rare Mutations of Two Presynaptic Cytomatrix Genes <i>BSN</i> and <i>PCLO</i> in Schizophrenia and Bipolar Disorder10.3390/jpm111110572075-4426https://doaj.org/article/246103831b9e46b2a32a8d2e4c3474bc2021-10-01T00:00:00Zhttps://www.mdpi.com/2075-4426/11/11/1057https://doaj.org/toc/2075-4426Schizophrenia and bipolar disorder are severe mental disorders with a major component of genetic factors in their etiology. Rare mutations play a significant role in these two disorders, and they are highly heterogeneous and personalized. Identification of personalized mutations is essential for the establishment of molecular diagnosis, providing insight into pathogenesis and guiding the personalized treatment for each affected patient. We conducted whole-genome sequencing analysis of families with schizophrenia and bipolar disorder to search for their genetic underpinnings. This report identified a rare missense mutation Arg1087Gln of <i>BSN</i> (bassoon presynaptic cytomatrix protein) co-segregating with schizophrenia in a family with multiple affected members. Furthermore, we identified the rare missense mutation Ser1535Leu of <i>PCLO</i> (piccolo presynaptic cytomatrix protein) in two sisters with bipolar disorder and another rare missense mutation, His5142Arg in <i>PCLO</i>, in a patient with schizophrenia. These three missense mutations were very rare and were predicted to be pathogenic. The <i>BSN</i> and <i>PCLO</i> genes encode two structurally related proteins of the presynaptic cytomatrix at the active zone that regulates neurotransmission at the presynaptic neuronal terminal. Our findings suggest the involvement of the presynaptic matrix in the pathogenesis of schizophrenia and bipolar disorder, and <i>BSN</i> and <i>PCLO</i> are the risk genes for schizophrenia and bipolar disorder.Chia-Hsiang ChenYu-Shu HuangDing-Lieh LiaoCheng-Yi HuangChia-Heng LinTing-Hsuan FangMDPI AGarticleschizophreniabipolar disorderpresynaptic cytomatrixactive zoneneurotransmissionMedicineRENJournal of Personalized Medicine, Vol 11, Iss 1057, p 1057 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	schizophrenia bipolar disorder presynaptic cytomatrix active zone neurotransmission Medicine R
spellingShingle	schizophrenia bipolar disorder presynaptic cytomatrix active zone neurotransmission Medicine R Chia-Hsiang Chen Yu-Shu Huang Ding-Lieh Liao Cheng-Yi Huang Chia-Heng Lin Ting-Hsuan Fang Identification of Rare Mutations of Two Presynaptic Cytomatrix Genes <i>BSN</i> and <i>PCLO</i> in Schizophrenia and Bipolar Disorder
description	Schizophrenia and bipolar disorder are severe mental disorders with a major component of genetic factors in their etiology. Rare mutations play a significant role in these two disorders, and they are highly heterogeneous and personalized. Identification of personalized mutations is essential for the establishment of molecular diagnosis, providing insight into pathogenesis and guiding the personalized treatment for each affected patient. We conducted whole-genome sequencing analysis of families with schizophrenia and bipolar disorder to search for their genetic underpinnings. This report identified a rare missense mutation Arg1087Gln of <i>BSN</i> (bassoon presynaptic cytomatrix protein) co-segregating with schizophrenia in a family with multiple affected members. Furthermore, we identified the rare missense mutation Ser1535Leu of <i>PCLO</i> (piccolo presynaptic cytomatrix protein) in two sisters with bipolar disorder and another rare missense mutation, His5142Arg in <i>PCLO</i>, in a patient with schizophrenia. These three missense mutations were very rare and were predicted to be pathogenic. The <i>BSN</i> and <i>PCLO</i> genes encode two structurally related proteins of the presynaptic cytomatrix at the active zone that regulates neurotransmission at the presynaptic neuronal terminal. Our findings suggest the involvement of the presynaptic matrix in the pathogenesis of schizophrenia and bipolar disorder, and <i>BSN</i> and <i>PCLO</i> are the risk genes for schizophrenia and bipolar disorder.
format	article
author	Chia-Hsiang Chen Yu-Shu Huang Ding-Lieh Liao Cheng-Yi Huang Chia-Heng Lin Ting-Hsuan Fang
author_facet	Chia-Hsiang Chen Yu-Shu Huang Ding-Lieh Liao Cheng-Yi Huang Chia-Heng Lin Ting-Hsuan Fang
author_sort	Chia-Hsiang Chen
title	Identification of Rare Mutations of Two Presynaptic Cytomatrix Genes <i>BSN</i> and <i>PCLO</i> in Schizophrenia and Bipolar Disorder
title_short	Identification of Rare Mutations of Two Presynaptic Cytomatrix Genes <i>BSN</i> and <i>PCLO</i> in Schizophrenia and Bipolar Disorder
title_full	Identification of Rare Mutations of Two Presynaptic Cytomatrix Genes <i>BSN</i> and <i>PCLO</i> in Schizophrenia and Bipolar Disorder
title_fullStr	Identification of Rare Mutations of Two Presynaptic Cytomatrix Genes <i>BSN</i> and <i>PCLO</i> in Schizophrenia and Bipolar Disorder
title_full_unstemmed	Identification of Rare Mutations of Two Presynaptic Cytomatrix Genes <i>BSN</i> and <i>PCLO</i> in Schizophrenia and Bipolar Disorder
title_sort	identification of rare mutations of two presynaptic cytomatrix genes <i>bsn</i> and <i>pclo</i> in schizophrenia and bipolar disorder
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/246103831b9e46b2a32a8d2e4c3474bc
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Identification of Rare Mutations of Two Presynaptic Cytomatrix Genes <i>BSN</i> and <i>PCLO</i> in Schizophrenia and Bipolar Disorder

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