Screening for inborn errors of metabolism in psychotic patients using Next Generation Sequencing

Nikita van de Burgt, Silvana van Koningsbruggen, Leonie Behrens, Nicole Leibold, Pilar Martinez Martinez, Marcel Mannens, Thérèse van Amelsvoort

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Abstract

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.
Original languageEnglish
Pages (from-to)125-129
Number of pages5
JournalJournal of Psychiatric Research
Volume138
DOIs
Publication statusPublished - Jun 2021

Keywords

  • gene variants
  • genetic disorders
  • inborn errors of metabolism
  • next generation sequencing
  • psychosis
  • ACUTE INTERMITTENT PORPHYRIA
  • HOMOCYSTEINE
  • DIAGNOSIS
  • Inborn errors of metabolism
  • Genetic disorders
  • Gene variants
  • SECONDARY
  • DISORDERS
  • Next generation sequencing
  • Psychosis
  • WILSONS-DISEASE
  • PICK TYPE-C
  • MUTATIONS
  • HOMOCYSTINURIA
  • MANIFESTATIONS

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