TY - JOUR
T1 - Screening for inborn errors of metabolism in psychotic patients using Next Generation Sequencing
AU - van de Burgt, Nikita
AU - van Koningsbruggen, Silvana
AU - Behrens, Leonie
AU - Leibold, Nicole
AU - Martinez-Martinez, Pilar
AU - Mannens, Marcel
AU - van Amelsvoort, Therese
N1 - Funding Information: This study was funded by Actelion . The funders had no further role in the study design, the data collection, analysis and interpretation of the data. Additionally, the funders had no role in the writing of the report and the decision to submit the paper for publication. Publisher Copyright: © 2021 The Author(s)
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Inborn errors of metabolism (IEMs) are a group of rare genetic disorders which, when emerging later in life, are often characterized by neuropsychiatric manifestations including psychosis. This study aimed to determine whether it would be useful to screen patients presenting with a psychotic disorder for IEMs by a single blood sample using Next Generation Sequencing (NGS), in order to detect rare, treatable causes of psychotic disorders. Blood was drawn from 60 patients with a psychotic disorder, with a duration of illness of less than 5 years. Blood samples were screened for 67 genes using NGS (Illumina® MiSeq sequencing technique). The results were compared to the human reference genome (GoNL, n = 498). The identified variants were classified according to the ACMG classification. For the psychotic patients, 6 variants of a likely pathogenic (class 4, n = 2) or pathogenic (class 5, n = 4) origin were found. As all variants were heterozygous, no patients were considered to be affected by an IEM. For the GoNL control group, 73 variants of a likely pathogenic (class 4, n = 31) or pathogenic (class 5, n = 42) origin were found. All of these found variants were heterozygous. Therefore, these individuals from the control group were considered to be a carrier only. Thus, no patients were identified to have an IEM as an underlying disease using this approach. However, NGS may be useful to detect variants of genes associated with IEMs in an enriched subgroup of psychotic patients.
AB - Inborn errors of metabolism (IEMs) are a group of rare genetic disorders which, when emerging later in life, are often characterized by neuropsychiatric manifestations including psychosis. This study aimed to determine whether it would be useful to screen patients presenting with a psychotic disorder for IEMs by a single blood sample using Next Generation Sequencing (NGS), in order to detect rare, treatable causes of psychotic disorders. Blood was drawn from 60 patients with a psychotic disorder, with a duration of illness of less than 5 years. Blood samples were screened for 67 genes using NGS (Illumina® MiSeq sequencing technique). The results were compared to the human reference genome (GoNL, n = 498). The identified variants were classified according to the ACMG classification. For the psychotic patients, 6 variants of a likely pathogenic (class 4, n = 2) or pathogenic (class 5, n = 4) origin were found. As all variants were heterozygous, no patients were considered to be affected by an IEM. For the GoNL control group, 73 variants of a likely pathogenic (class 4, n = 31) or pathogenic (class 5, n = 42) origin were found. All of these found variants were heterozygous. Therefore, these individuals from the control group were considered to be a carrier only. Thus, no patients were identified to have an IEM as an underlying disease using this approach. However, NGS may be useful to detect variants of genes associated with IEMs in an enriched subgroup of psychotic patients.
KW - Gene variants
KW - Genetic disorders
KW - Inborn errors of metabolism
KW - Next generation sequencing
KW - Psychosis
UR - http://www.scopus.com/inward/record.url?scp=85103972504&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jpsychires.2021.03.060
DO - https://doi.org/10.1016/j.jpsychires.2021.03.060
M3 - Article
C2 - 33848968
SN - 0022-3956
VL - 138
SP - 125
EP - 129
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
ER -