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. 2021 Jan 12:11:606372.
doi: 10.3389/fpsyt.2020.606372. eCollection 2020.

CNVs and Chromosomal Aneuploidy in Patients With Early-Onset Schizophrenia and Bipolar Disorder: Genotype-Phenotype Associations

Hojka Gregoric Kumperscak  1   2 , Danijela Krgovic  2   3 , Maja Drobnic Radobuljac  4   5 , Nina Senica  1 , Andreja Zagorac  3 , Nadja Kokalj Vokac  2   3
Affiliations

CNVs and Chromosomal Aneuploidy in Patients With Early-Onset Schizophrenia and Bipolar Disorder: Genotype-Phenotype Associations

Hojka Gregoric Kumperscak et al. Front Psychiatry. .

Abstract

Introduction: Early-onset schizophrenia (EOS) and bipolar disorder (EOB) start before the age of 18 years and have a more severe clinical course, a worse prognosis, and a greater genetic loading compared to the late-onset forms. Copy number variations (CNVs) are an important genetic factor in the etiology of psychiatric disorders. Therefore, this study aimed to analyze CNVs in patients with EOS and EOB and to establish genotype-phenotype relationships for contiguous gene syndromes or genes affected by identified CNVs. Methods: Molecular karyotyping was performed in 45 patients, 38 with EOS and seven with EOB hospitalized between 2010 and 2017. The exclusion criteria were medical or neurological disorders or IQ under 70. Detected CNVs were analyzed according to the standards and guidelines of the American College of Medical Genetics. Result: Molecular karyotyping showed CNVs in four patients with EOS (encompassing the PAK2, ADAMTS3, and ADAMTSL1 genes, and the 16p11.2 microduplication syndrome) and in two patients with EOB (encompassing the ARHGAP11B and PRODH genes). In one patient with EOB, a chromosomal aneuploidy 47, XYY was found. Discussion: Our study is the first study of CNVs in EOS and EOB patients in Slovenia. Our findings support the association of the PAK2, ARHGAP11B, and PRODH genes with schizophrenia and/or bipolar disorder. To our knowledge, this is also the first report of a multiplication of the ADAMTSL1 gene and the smallest deletion of the PAK2 gene in a patient with EOS, and one of the few reports of the 47, XYY karyotype in a patient with EOB.

Keywords: bipolar disorder; chromosomal aneuploidy; copy number variations; early onset; schizophrenia.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Molecular karyotyping of Patient 1 demonstrating deletion in 3q29 region, [GRCh37] 3q29(196534625_196599109)X1 (A), which resulted in the partial deletion of the PAK2 and SENP5 genes (B), according to UCSC Genome Browser (C).
Figure 2
Figure 2
Molecular karyotyping of Patient 2 demonstrating duplication in 15q25.2 region, [GRCh37] 15q25.2(82769959_84812664)X3 (A), encompasses 11 OMIM genes (Table 1), including ADAMTS3 gene (B), according to UCSC Genome Browser (C).
Figure 3
Figure 3
Molecular karyotyping of Patient 4 demonstrating multiplication in 9p22 region, [GRCh37]9p22.2p22.1(17841908_18515947)X4~5 (A), encompassing ADAMTSL1 gene (B), according to UCSC Genome Browser (C).
Figure 4
Figure 4
Molecular karyotyping of Patient 5 demonstrating duplication in 16p11.2 region, [GRCh37] 16p11.2(29673984_30197316)X3 (A), which included the recurrent breakpoint (BP) regions BP4 and BP5 (B), according to UCSC Genome Browser (C).
Figure 5
Figure 5
Molecular karyotyping of Patient 3 demonstrating duplication in 15q13.2 region, [GRCh37] 15q13.2(30819487_31089960)X3 (A), encompassing ARHGAP11B gene (B), according to UCSC Genome Browser (C).
Figure 6
Figure 6
Molecular karyotyping of patient 6 demonstrating deletion in 22q11.21 region,[GRCh37] 22q11.21(18706023_19010479)X1 (A), encompasses the DGCR6, PRODH genes, and the first four exons of the DGCR5 gene (B), according to UCSC Genome Browser (C).
Figure 7
Figure 7
Molecular karyotyping of patient 7 demonstrating complete duplication of chromosome Y,[GRCh37] (X)x1,(Y)x2 (A,B), which resulted in 47,XYY karyotype.
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