Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Faculty of Health and Life Sciences (FHML), Maastricht University, Maastricht, the Netherlands.
Department of Clinical Genetics, Laboratory of Genome Diagnostics, Amsterdam University Medical Centre (AUMC), Amsterdam, the Netherlands.
J Psychiatr Res. 2021 Jun;138:125-129. doi: 10.1016/j.jpsychires.2021.03.060. Epub 2021 Apr 1.
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.
先天性代谢缺陷（IEMs）是一组罕见的遗传疾病，当它们在生命后期出现时，常伴有神经精神表现，包括精神病。本研究旨在通过单次血液样本使用下一代测序（NGS）来确定对出现精神病的患者进行 IEM 筛查是否有用，以便检测罕见的、可治疗的精神病原因。从 60 名患有精神病且病程少于 5 年的患者中抽取血液样本。使用 NGS（Illumina® MiSeq 测序技术）对 67 个基因进行了筛查。将结果与人类参考基因组（GoNL，n=498）进行比较。根据 ACMG 分类法对鉴定出的变异进行分类。对于精神病患者，发现了 6 种可能具有致病性（4 类，n=2）或致病性（5 类，n=4）来源的变体。由于所有变体均为杂合子，因此没有患者被认为患有 IEM。对于 GoNL 对照组，发现了 73 种可能具有致病性（4 类，n=31）或致病性（5 类，n=42）来源的变体。所有这些发现的变体均为杂合子。因此，这些对照组个体仅被认为是携带者。因此，使用这种方法未发现任何患者存在 IEM 作为潜在疾病。然而，NGS 可能有助于在精神病患者的富集亚组中检测与 IEM 相关的基因变异。
