Genetic Analysis for Two Italian Siblings with Usher Syndrome and Schizophrenia

Domanico, Daniela; Fragiotta, Serena; Trabucco, Paolo; Nebbioso, Marcella

doi:10.1155/2012/380863

Cited by 14 publications

(15 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The trend we observed for an increased rate of de novo CNVs in BD compared with controls is consistent with a small proportion of these loci playing a role in the pathogenesis of the disorder. The more likely candidate loci are the following: the deletion at DLG2 , a gene implicated in SZ ( 24 ) and BD ( 23 ); the duplication at 16p11.2, as it is also implicated in SZ and BD ( 13 , 21 ) [our proband with de novo duplication was among the cases used in the original case–control study that found an association with BD ( 13 )]; the duplication of the ‘distal 16p11.2’ locus, as it is an ID locus, while the reciprocal deletion is both an SZ and ID locus ( 15 , 27 ); the deletion at PCDH15 , as mutations in this gene can cause deafness and Usher syndrome Type IF ( ), a disorder with a possibly increased rate of psychosis and behavioural problems ( 28 , 29 ).…”

Section: Discussionmentioning

confidence: 99%

De novo CNVs in bipolar affective disorder and schizophrenia

Georgieva

Rees

Moran

et al. 2014

Human Molecular Genetics

View full text Add to dashboard Cite

An increased rate of de novo copy number variants (CNVs) has been found in schizophrenia (SZ), autism and developmental delay. An increased rate has also been reported in bipolar affective disorder (BD). Here, in a larger BD sample, we aimed to replicate these findings and compare de novo CNVs between SZ and BD. We used Illumina microarrays to genotype 368 BD probands, 76 SZ probands and all their parents. Copy number variants were called by PennCNV and filtered for frequency (<1%) and size (>10 kb). Putative de novo CNVs were validated with the z-score algorithm, manual inspection of log R ratios (LRR) and qPCR probes. We found 15 de novo CNVs in BD (4.1% rate) and 6 in SZ (7.9% rate). Combining results with previous studies and using a cut-off of >100 kb, the rate of de novo CNVs in BD was intermediate between controls and SZ: 1.5% in controls, 2.2% in BD and 4.3% in SZ. Only the differences between SZ and BD and SZ and controls were significant. The median size of de novo CNVs in BD (448 kb) was also intermediate between SZ (613 kb) and controls (338 kb), but only the comparison between SZ and controls was significant. Only one de novo CNV in BD was in a confirmed SZ locus (16p11.2). Sporadic or early onset cases were not more likely to have de novo CNVs. We conclude that de novo CNVs play a smaller role in BD compared with SZ. Patients with a positive family history can also harbour de novo mutations.

show abstract

Section: Discussionmentioning

confidence: 99%

De novo CNVs in bipolar affective disorder and schizophrenia

Georgieva

Rees

Moran

et al. 2014

Human Molecular Genetics

View full text Add to dashboard Cite

show abstract

“…Recently, a 386‐kb deletion on 10q21.1, including the first three exons of PCDH15 , was reported in a subject with autism spectrum disorder (Sorte et al ). Although primarily recognized as a disease associated with deafness and blindness, more than 20% of Usher syndrome patients display psychiatric symptoms (Carvill ) and comorbidities of Usher syndrome with various mental illnesses are well documented (Domanico et al ; Rao et al ; Rijavec & Grubic ). Our findings suggest that there may be genetic components that underlie these symptoms and that relate to perturb 5‐HT signaling, though further studies are needed to assess possible relationships.…”

Section: Discussionmentioning

confidence: 99%

Quantitative trait loci mapping and gene network analysis implicate protocadherin‐15 as a determinant of brain serotonin transporter expression

Carneiro

Han

et al. 2014

Genes Brain and Behavior

View full text Add to dashboard Cite

Presynaptic serotonin (5-hydroxytryptamine, 5-HT) transporters (SERT) regulate 5-HT signaling via antidepressant-sensitive clearance of released neurotransmitter. Polymorphisms in the human SERT gene (SLC6A4) have been linked to risk for multiple neuropsychiatric disorders, including depression, obsessive-compulsive disorder and autism. Using BXD recombinant inbred mice, a genetic reference population that can support the discovery of novel determinants of complex traits, merging collective trait assessments with bioinformatics approaches, we examine phenotypic and molecular networks associated with SERT gene and protein expression. Correlational analyses revealed a network of genes that significantly associated with SERT mRNA levels. We quantified SERT protein expression levels and identified region- and gender-specific quantitative trait loci (QTLs), one of which associated with male midbrain SERT protein expression, centered on the protocadherin-15 gene (Pcdh15), overlapped with a QTL for midbrain 5-HT levels. Pcdh15 was also the only QTL-associated gene whose midbrain mRNA expression significantly associated with both SERT protein and 5-HT traits, suggesting an unrecognized role of the cell adhesion protein in the development or function of 5-HT neurons. To test this hypothesis, we assessed SERT protein and 5-HT traits in the Pcdh15 functional null line (Pcdh15av-3J), studies that revealed a strong, negative influence of Pcdh15 on these phenotypes. Together, our findings illustrate the power of multidimensional profiling of recombinant inbred lines in the analysis of molecular networks that support synaptic signaling, and that, as in the case of Pcdh15, can reveal novel relationships that may underlie risk for mental illness.

show abstract

“…Moreover, the interaction between RUNX2 and VDR (the 1α,25-dihydroxyvitamin D3 receptor) regulates the expression of both SPAG5 and SRGAP3 (Stephens and Morrison 2014). SPAG5 has been selected in AMHs (Green et al 2010) and encodes an interactor of the isoform B of USH2A (Kersten et al 2012), the main candidate for Usher syndrome, a condition involving combined deaf-blindness and occasional schizophrenia-like symptoms (Domanico et al 2012; see Leivada and Boeckx 2014 for detailed discussion). In turn, SRGAP3 is related to both schizophrenia ) and severe mental retardation and absence of speech (Endris et al 2002).…”

Section: Core Candidate Genes For Language Evolutionmentioning

confidence: 99%

Bridging the gap between genes and language deficits in schizophrenia: an oscillopathic approach

Murphy

Benítez‐Burraco

2016

Preprint

View full text Add to dashboard Cite

Schizophrenia is characterized by marked language deficits, but it is not clear how these deficits arise from the alteration of genes related to the disease. The goal of this paper is to aid the bridging of the gap between genes and schizophrenia and, ultimately, give support to the view that the abnormal presentation of language in this condition is heavily rooted in the evolutionary processes that brought about modern language. To that end we will focus on how the schizophrenic brain processes language and, particularly, on its distinctive oscillatory profile during language processing. Additionally, we will show that candidate genes for schizophrenia are overrepresented among the set of genes that are believed to be important for the evolution of the human faculty of language. These genes crucially include (and are related to) genes involved in brain rhythmicity. We will claim that this translational effort and the links we uncover may help develop an understanding of language evolution, along with the etiology of schizophrenia, its clinical/linguistic profile, and its high prevalence among modern populations.

show abstract

Genetic Analysis for Two Italian Siblings with Usher Syndrome and Schizophrenia

Cited by 14 publications

References 14 publications

De novo CNVs in bipolar affective disorder and schizophrenia

De novo CNVs in bipolar affective disorder and schizophrenia

Quantitative trait loci mapping and gene network analysis implicate protocadherin‐15 as a determinant of brain serotonin transporter expression

Bridging the gap between genes and language deficits in schizophrenia: an oscillopathic approach

Contact Info

Product

Resources

About