A balanced translocation disrupting BCL2L10 and PNLDC1 segregates with affective psychosis

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.

[1]  G. Kirov,et al.  Copy number variation in bipolar disorder , 2015, Molecular Psychiatry.

[2]  J. Potash,et al.  Metamoodics: meta-analysis and bioinformatics resource for mood disorders , 2014, Molecular Psychiatry.

[3]  Eric S. Lander,et al.  A polygenic burden of rare disruptive mutations in schizophrenia , 2014, Nature.

[4]  C. Clements,et al.  Suicide in bipolar disorder in a national English sample, 1996–2009: frequency, trends and characteristics , 2013, Psychological Medicine.

[5]  J. Guérin,et al.  Subcellular dynamics of the maternal cell death regulator BCL2L10 in human preimplantation embryos. , 2013, Human reproduction.

[6]  A. Virtanen,et al.  Poly(A)-specific ribonuclease (PARN): An allosterically regulated, processive and mRNA cap-interacting deadenylase , 2013, Critical reviews in biochemistry and molecular biology.

[7]  Hongyu Zhao,et al.  Increased ratio of anti-apoptotic to pro-apoptotic Bcl2 gene-family members in lithium-responders one month after treatment initiation , 2012, Biology of Mood & Anxiety Disorders.

[8]  D. Bentley,et al.  Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4 , 2012, Nature Genetics.

[9]  Patrick F. Sullivan,et al.  Genetic architectures of psychiatric disorders: the emerging picture and its implications , 2012, Nature Reviews Genetics.

[10]  Pamela B. Mahon,et al.  Meta‐analysis of genetic association studies on bipolar disorder , 2012, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[11]  M. Karayiorgou.  THE GENETIC ARCHITECTURE OF SCHIZOPHRENIA: NEW MUTATIONS AND EMERGING PARADIGMS , 2012, Schizophrenia Research.

[12]  M. Karayiorgou,et al.  The genetic architecture of schizophrenia: new mutations and emerging paradigms. , 2012, Annual review of medicine.

[13]  Daniel L. Koller,et al.  Genome Wide Linkage Analysis of 972 Bipolar Pedigrees Using Single Nucleotide Polymorphisms , 2011, Molecular Psychiatry.

[14]  J. Suvisaari,et al.  Quality of life of people with schizophrenia, bipolar disorder and other psychotic disorders , 2010, British Journal of Psychiatry.

[15]  Jessica C. Ebert,et al.  Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA Nanoarrays , 2010, Science.

[16]  Eun-Young Kim,et al.  Role of Bcl2-like 10 (Bcl2l10) in Regulating Mouse Oocyte Maturation1 , 2009, Biology of reproduction.

[17]  G. Gillet,et al.  Oocytes and early embryos selectively express the survival factor BCL2L10 , 2009, Journal of Molecular Medicine.

[18]  Leena Peltonen,et al.  Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. , 2003, American journal of human genetics.

[19]  D. Blackwood,et al.  Chromosomal abnormalities and mental illness , 2003, Molecular Psychiatry.

[20]  S. Cory,et al.  The Bcl2 family: regulators of the cellular life-or-death switch , 2002, Nature Reviews Cancer.

[21]  W. Holzgreve,et al.  Bcl2-L-10, a novel anti-apoptotic member of the Bcl-2 family, blocks apoptosis in the mitochondria death pathway but not in the death receptor pathway. , 2001, Human molecular genetics.

[22]  M. Polymeropoulos,et al.  Mapping of a Gene for Parkinson's Disease to Chromosome 4q21-q23 , 1996, Science.

[23]  E. Wijsman,et al.  Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region. , 1992, American journal of human genetics.

[24]  J. Haines,et al.  Assessment of amyloid beta-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases. , 1992, American journal of human genetics.

[25]  M. Pericak-Vance,et al.  Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease , 1991, Nature.

[26]  J W Gray,et al.  Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R. Bannerman,et al.  Recurrent pregnancy losses and parental chromosome abnormalities: a review , 1985, British journal of obstetrics and gynaecology.

[28]  J. Suvisaari,et al.  Lifetime prevalence of psychotic and bipolar I disorders in a general population. , 2007, Archives of general psychiatry.

[29]  M. Baron,et al.  Manic-depression genes and the new millennium: poised for discovery , 2002, Molecular Psychiatry.