Psychiatric syndromes in individuals with chromosome 18 abnormalities

Department of Psychiatry, South Texas Psychiatric Genetics Research Center, University of Texas Health Science Center at San Antonio, 454 Soledad, Suite 200, San Antonio, TX 78205, USA.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.42). 01/2009; 153B(3):837-45. DOI: 10.1002/ajmg.b.31047
Source: PubMed


Chromosome 18 abnormalities are associated with a range of physical abnormalities such as short stature and hearing impairments. Psychiatric manifestations have also been observed. This study focuses on the presentations of psychiatric syndromes as they relate to specific chromosomal abnormalities of chromosome 18. Twenty-five subjects (13 with an 18q deletion, 9 with 18p tetrasomy, and 3 with an 18p deletion), were interviewed by psychiatrists (blind to specific chromosomal abnormality) using the DIGS (subjects 18 and older) or KSADS-PL (subjects under 18). A consensus best estimation diagnostic process was employed to determine psychiatric syndromes. Oligonucleotide Array Comparative Genomic Hybridization (Agilent Technologies) was utilized to define specific regions of chromosome 18 that were deleted or duplicated. These data were further analyzed to determine critical regions of the chromosome as they relate to phenotypic manifestations in these subjects. 58.3% of the chromosome 18q- deletion subjects had depressive symptoms, 58.3% had anxiety symptoms, 25% had manic symptoms, and 25% had psychotic symptoms. 66.6% of the chromosome 18p- deletion subjects had anxiety symptoms, and none had depressive, manic, or psychotic symptoms. Fifty percent of the chromosome 18p tetrasomy subjects had anxiety symptoms, 12.5% had psychotic symptoms, and 12.5% had a mood disorder. All three chromosomal disorders were associated with high anxiety rates. Psychotic, manic and depressive disorders were seen mostly in 18q- subjects and this may be helpful in narrowing regions for candidate genes for these psychiatric conditions.

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    • "Therefore, altered levels of NDUFV2 may be involved in episodes of depression and mania. At the molecular level, NDUFV2 is located on chromosome 18, harboring genetic susceptibility loci for schizophrenia and affective disorders (Camp et al., 2005; Chavarria-Siles et al., 2007; Detera-Wadleigh et al., 1999; Zavala et al., 2010). Accordingly, we hypothesized that NDUFV2 may also be a susceptibility gene for MDD, aside from schizophrenia and BD. "
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    ABSTRACT: Background: There is ample evidence supporting the idea that mitochondrial dysfunction and altered expression of complex I subunits play important roles in the pathophysiology of mental disorders. Early literature reports have implicated NDUFV2, a nuclear-encoded mitochondrial complex I subunit gene, in bipolar disorder and schizophrenia. There has been no genetic study to investigate whether there is an association between NDUFV2 and major depressive disorder (MDD). Methods: This study recruited 744 patients with MDD and 767 well-matched healthy controls in a Chinese Han population, and genotyped 9 SNPs within NDUFV2. Results: Initial analysis showed statistically significant differences for 2 SNPs (rs4798765 and rs12964485) in the genotypic distribution and for 1 SNP (rs4797356) in the allelic distribution between the case and control groups. Nevertheless, no significance was demonstrated following multiple testing corrections. Haplotype analysis showed that the T-C haplotype, consisting of rs12457810 and rs12964485, was significantly associated with MDD (P=0.005, corrected P=0.04 after a 10,000 permutation test). We performed an eQTL analysis and found that rs12964485 was significantly associated with NDUFV2 expression in the occipital cortex (P=0.036), albeit this significance did not survive after Bonferroni correction. Limitation: This is a preliminary investigation with a relatively modest sample size. Conclusion: Our findings provided preliminary evidence that a haplotype T-C consisting of rs12457810 and rs12964485 in the 5'-upstream region of NDUFV2 may be a protective factor for the development of MDD in Han Chinese.
    Full-text · Article · Oct 2015 · Journal of Affective Disorders
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    • "Submicroscopic 18p deletions were already reported. Recently published cases with abnormal phenotype that were tested with array involve larger terminal abnormalities [9,10]. Terminal deletions found by using subtelomeric FISH probe or subtelomeric MLPA are also difficult to compare with our patient who has an interstitial submicroscopic aberration and normal subtelomeric regions (Figure 1) [11]. "
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    ABSTRACT: Background Recent development of MLPA (Multiplex-Ligation-dependent Probe Amplification, MRC-Holland) and microarray technology allows detection of a wide range of new submicroscopic abnormalities. Publishing new cases and case reviews associated with both clinical abnormalities and a normal phenotype is of great value. Findings/results We report on two phenotypically normal foetuses carrying a maternally-inherited interstitial submicroscopic abnormality of chromosome 18p11.32. Both abnormalities were found with the aneuploidy MLPA kit P095 during rapid aneuploidy detection, which was offered along with conventional karyotyping. Foetus 1 and its mother have a 1,7 Mb deletion and foetus 2 and its mother have a 1,9 Mb duplication. In both cases normal babies were born. We used the HumanCytoSNP-12 array of Illumina to visualize the CNVs and map the breakpoints. Conclusions We suggest that a CNV at 18p11.32 (528,050-2,337,486) may represent a new benign euchromatic variant.
    Full-text · Article · Dec 2011 · Molecular Cytogenetics
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    • "Ocular anomalies such as strabismus, anterior optic segment malformations, nystagmus and myopia have also been reported in several patients [15,16]. A variety of neurological malformations and disorders are also part of the syndrome: myelination disturbances, absent corpus callosus, holoprosencephaly, seizures and EEG pattern anomalies and psychiatric disorders (Rett syndrome, autism, depression, anxiety, mania, psychosis) [17-20]. "
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    ABSTRACT: Cystic Fibrosis (CF) is the most frequent recessive disease of Caucasian patients. Association with other diseases or syndromes has previously been reported. Co-morbidity may be a challenge for clinicians, who have to face more severe problems. We have described a CF infant, F508del homozygote, diagnosed by neonatal screening, who also had a chromosome 18q terminal deletion [del (18)(q22-qter)]. Some clinical features of the 18q deletion: e.g., cardiopathy, gastro-oesophageal reflux and severe muscular hypotonia, worsened the CF clinical picture and his quality of life, with repeated pulmonary exacerbations and failure to thrive in the first six months of life. The treatment strategy was chosen following an accurate multi-disciplinary team study of overlapping chromosome syndrome and CF symptoms. The use of a gastrostomy device for enteral nutrition together with a new device (Ez-PAP) for chest physiotherapy led to normal growth, a notably reduced hospitalization rate and improved quality of life. This case shows how co-morbidities worsening the clinical course of a "complicated patient" can be faced thanks to unconventional therapies that represent a challenge for clinicians.
    Full-text · Article · May 2011 · Italian Journal of Pediatrics
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