Isochromosome 13 in a patient with childhood-onset schizophrenia, ADHD, and motor tic disorder

Molecular Cytogenetics

Sherry Leonard¹  Randall G Ross⁴  Marianne Z Wamboldt³  Billie J Carstens²  Kirsten Floyd⁴  Karen Swisshelm²  Sharon L Graw⁴ 

[1] Research Division, Veterans Affairs Medical Research Service, Denver, CO, USA;Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, Aurora, CO, USA;Department of Psychiatry and Behavioral Science, Children's Hospital Colorado, Aurora, CO, USA;Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, USA

关键词: childhood;    Schizophrenia;    Isochromosome;    Chromosome 13;    Attention deficit hyperactivity disorder;   

Others  :  1151936
DOI  :  10.1186/1755-8166-5-2

 received in 2011-08-25, accepted in 2012-01-03,  发布年份 2012

【 摘 要 】

Background

A 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.

Results

Karyotypic analysis found 45,XX,i(13)(q10) 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.

Conclusions

We 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,i(13)(q10q10) 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.

【 授权许可】

   
2012 Graw et al; licensee BioMed Central Ltd.

【 图 表 】

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