Identification and characterization of three inherited genomic copy number variations associated with familial schizophrenia.
Schizophrenia is a complex mental disorder with high degree of genetic influence in its etiology. Several recent studies revealed that copy number variations (CNVs) of genomic DNA contributed significantly to the genetic architecture of sporadic schizophrenia. This study aimed to investigate whether CNVs also contribute to the familial forms of schizophrenia. Using array-based comparative genomic hybridization technology, we searched for pathogenic CNV associated with schizophrenia in a sample of 60 index cases from multiplex schizophrenia families. We detected three inherited CNVs that were associated with schizophrenia in three families, including a microdeletion of ~4.4Mb at chromosome 6q12-q13, a microduplication of ~1Mb at chromosome 18q12.3, and an interstitial duplication of ~5Mb at chromosome 15q11.2-q13.1. Our data indicate that CNVs contribute to the genetic underpinnings of the familial forms of schizophrenia as well as of the sporadic form. As 15q11-13 duplication is a well-known recurrent CNV associated with autism in the literature, the detection of the 15q11.2-q13.1 duplication in our schizophrenia patients provides additional support to other studies reporting that schizophrenia is part of the clinical spectrum of 15q11-q13 duplication syndrome.
Institute of Biotechnology and Graduate Program of Biotechnology in Medicine, National Tsing-Hua University, Hsinchu, Taiwan.
Hsiao-Mei
HM
Liao
Yu-Lin
YL
Chao
Ai-Ling
AL
Huang
Min-Chih
MC
Cheng
Yann-Jang
YJ
Chen
Kuei-Fang
KF
Lee
Jye-Siung
JS
Fang
Chih-Hao
CH
Hsu
Chia-Hsiang
CH
Chen
D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis; D056915:DNA Copy Number Variations / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000235:genetics*; D013624:Taiwan; D014314:Trisomy / Q000235:genetics