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Molecular Cytogenetics

, 5:2

First Online: 03 January 2012Received: 25 August 2011Accepted: 03 January 2012


BackgroundA small percentage of all cases of schizophrenia have a childhood onset. The impact on the individual and family can be devastating. We report the results of genetic analyses from a patient with onset of visual hallucinations at 5 years, and a subsequent diagnosis at 9 years of schizophrenia, attention deficit hyperactivity disorder ADHD with hyperactivity and impulsivity, and chronic motor tic disorder.

ResultsKaryotypic analysis found 45,XX,i13q10 in all cells examined. Alpha satellite FISH of isochromosome 13 revealed a large unsplit centromeric region, interpreted as two centromeres separated by minimal or undetectable short-arm material or as a single monocentric centromere, indicating that the isochromosome likely formed post-zygotically by a short arm U-type or centromeric exchange. Characterization of chromosome 13 simple tandem repeats and Affymetrix whole-genome 6.0 SNP array hybridization found homozygosity for all markers, and the presence of only a single paternal allele in informative markers, consistent with an isodisomic isochromosome of paternal origin. Analysis of two chromosome 13 schizophrenia candidate genes, D-amino acid oxidase activator DAOA and 5-hydroxytryptamine serotonin receptor 2A 5-HTR2A, failed to identify non-synonymous coding mutations but did identify homozygous risk polymorphisms.

ConclusionsWe report a female patient with childhood-onset schizophrenia, ADHD, and motor tic disorder associated with an isodisomic isochromosome 13 of paternal origin and a 45,XX,i13q10q10 karyotype. We examined two potential mechanisms to explain chromosome 13 involvement in the patient-s pathology, including reduction to homozygosity of a paternal mutation and reduction to homozygosity of a paternal copy number variation, but were unable to identify any overtly pathogenic abnormality. Future studies may consider whether epigenetic mechanisms resulting from uniparental disomy UPD and the lack of chromosome 13 maternal alleles lead to the patient-s features.

KeywordsAttention deficit hyperactivity disorder Chromosome 13 Isochromosome Schizophrenia childhood List of abbreviationsADHDattention deficit hyperactivity disorder

ANK3ankyrin 3

ATP8A2ATPase, class I, type 8A, member 2

BLASTBasic local alignment search tool

bpbase pair

CACNA1Ccalcium channel, voltage-dependent, L type, Alpha-1C subunit

CHRFAM7ACHRNA7 cholinergic receptor, nicotinic, alpha 7, exons 5-10 and FAM7A family with sequence similarity 7A, exons A-E fusion

CHRNA7cholinergic receptor, nicotinic, alpha 7

CNVcopy number variation


DAOAD-amino acid oxidase activator

DISC1disrupted in schizophrenia 1

DSM-IVDiagnostic and Statistical Manual of Mental Disorders, 4 edition

DTNBP1dystrobrevin binding protein 1

EPN4epsin 4

FISHfluorescence in situ hybridization

GABAgamma-aminobutyric acid

GAD1glutamate decarboxylase 1

GRM3glutamate receptor, metabotropic 3

HTR2A5-hydroxytryptamine serotonin receptor 2A

ITIH3inter-alpha-trypsin inhibitor, heavy chain 3

ITIH4inter-alpha-trypsin inhibitor, heavy chain 4

LHFPlipoma HMGIC fusion partner

LOHloss of heterozygosity

MYT1Lmyelin transcription factor 1-like

NRG1neuregulin 1

NRXN1neurexin 1

PCRpolymerase chain reaction

PHF11PHD finger protein 11

PIBF1; C13orf24progesterone-induced blocking factor 1

PLAAphospholipase A2-activating protein

PRODHproline dehydrogenase oxidase 2

RCBTB1Regulator of chromosome condensation RCC1 and BTB POZ domain contain protein 1

SMAD5mothers against decapentaplegic, drosophila, homolog of, 5

SNPsingle nucleotide polymorphism

SPRY4sprout, drosophila, homolog of, 4

STRsimple tandem repeat

UPDuniparental disomy

UTRuntranslated region

VCFSvelocardiofacial syndrome

ZNF804Azinc finger protein 804A

Electronic supplementary materialThe online version of this article doi:10.1186-1755-8166-5-2 contains supplementary material, which is available to authorized users.

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Autor: Sharon L Graw - Karen Swisshelm - Kirsten Floyd - Billie J Carstens - Marianne Z Wamboldt - Randall G Ross - Sherry Leo


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