A balanced translocation disrupting BCL2L10 and PNLDC1 segregates with affective psychosis

Abstract

Affective psychoses are a group of severe psychiatric disorders, including schizoaffective disorder and bipolar I disorder, together affecting ∼1% of the population. Despite their high heritability, the molecular genetics and neurobiology of affective psychosis remain largely elusive. Here, we describe the identification of a structural genetic variant segregating with affective psychosis in a family with multiple members suffering from bipolar I disorder or schizoaffective disorder, bipolar type. A balanced translocation involving chromosomes 6 and 15 was detected by karyotyping and fluorescence in-situ hybridization (FISH). Using whole-genome sequencing, we rapidly delineated the translocation breakpoints as corresponding intragenic events disrupting BCL2L10 and PNLDC1. These data warrant further consideration for BCL2L10 and PNLDC1 as novel candidates for affective psychosis. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Keywords: BCL2L10; PNLDC1; affective psychosis; balanced translocation; bipolar disorder; cytogenetics; schizoaffective disorder; whole-genome sequencing.

Figure 1

Pedigree. The index patient (III‐4) is indicated with an arrow as the proband (P). Shaded symbols indicate family members with affective psychosis. Subjects from whom DNA was available are numbered. Plus (+) or minus (−) symbols indicate the presence or absence of the balanced translocation.

Figure 2

Cytogenetic studies. (A) Complete karyogram from subject III‐4 with the inherited balanced translocation: 46,XX,t(6;15)(q26;q21). (B) Selected karyogram images demonstrating the heterozygous abnormal representation of chromosome 6 (top row) and chromosome 15 (bottom row). (C and D) Fluorescence in‐situ hybridization showing the abnormalities in chromosome 6 (C) and chromosome 15 (D) indicated by the arrows. In (C), probes pertaining to chromosome 6 are labeled in red, and probes pertaining to chromosome 15 are labeled in green. In (D), probes pertaining to chromosome 15 are labeled in red, and probes pertaining to chromosome 6 are labeled in green. For both (C) and (D), chromosomes are visualized in blue.

Figure 3

Chromosomal rearrangement. (A) Schematic view of the balanced translocation involving chromosomes 6 and 15. (B) Electropherograms of the DNA sequence across the translocation breakpoints.