Chromosomal Microarray Analysis as First-Tier Genetic Test for Schizophrenia

Chen, Chia‐Hsiang; Cheng, Min-Chih; Hu, Tsung‐Ming; Ping, Lieh-Yung

doi:10.3389/fgene.2021.620496

Cited by 6 publications

(5 citation statements)

References 91 publications

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“…In routine practice, a diagnostic yield of~15% is reached for patients with IDD or MCA and can be attributed to large CNVs (>100 kb) 4. Despite the rapid adoption of next generation sequencing, standard chromosomal analysis and CMA remain the first-tier tests for most rare disorders diagnostic workup 5–9…”

Section: Introductionmentioning

confidence: 99%

Exome sequencing as a first-tier test for copy number variant detection: retrospective evaluation and prospective screening in 2418 cases

et al. 2022

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BackgroundDespite the availability of whole exome (WES) and genome sequencing (WGS), chromosomal microarray (CMA) remains the first-line diagnostic test in most rare disorders diagnostic workup, looking for copy number variations (CNVs), with a diagnostic yield of 10%–20%. The question of the equivalence of CMA and WES in CNV calling is an organisational and economic question, especially when ordering a WGS after a negative CMA and/or WES.MethodsThis study measures the equivalence between CMA and GATK4 exome sequencing depth of coverage method in detecting coding CNVs on a retrospective cohort of 615 unrelated individuals. A prospective detection of WES-CNV on a cohort of 2418 unrelated individuals, including the 615 individuals from the validation cohort, was performed.ResultsOn the retrospective validation cohort, every CNV detectable by the method (ie, a CNV with at least one exon not in a dark zone) was accurately called (64/64 events). In the prospective cohort, 32 diagnoses were performed among the 2418 individuals with CNVs ranging from 704 bp to aneuploidy. An incidental finding was reported. The overall increase in diagnostic yield was of 1.7%, varying from 1.2% in individuals with multiple congenital anomalies to 1.9% in individuals with chronic kidney failure.ConclusionCombining single-nucleotide variant (SNV) and CNV detection increases the suitability of exome sequencing as a first-tier diagnostic test for suspected rare Mendelian disorders. Before considering the prescription of a WGS after a negative WES, a careful reanalysis with updated CNV calling and SNV annotation should be considered.

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Section: Introductionmentioning

confidence: 99%

Exome sequencing as a first-tier test for copy number variant detection: retrospective evaluation and prospective screening in 2418 cases

et al. 2022

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“…These two families received CNV screening via chromosomal microarray analysis in our previous studies [31,32], but we did not detect rare pathogenic or likely pathogenic CNVs associated with their psychiatric conditions. Hence, they were further subjected to WGS analysis.…”

Section: Discussionmentioning

confidence: 93%

Whole Genome Sequencing Revealed Inherited Rare Oligogenic Variants Contributing to Schizophrenia and Major Depressive Disorder in Two Families

Chung

Huang

Fang

et al. 2023

IJMS

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Schizophrenia and affective disorder are two major complex mental disorders with high heritability. Evidence shows that rare variants with significant clinical impacts contribute to the genetic liability of these two disorders. Also, rare variants associated with schizophrenia and affective disorders are highly personalized; each patient may carry different variants. We used whole genome sequencing analysis to study the genetic basis of two families with schizophrenia and major depressive disorder. We did not detect de novo, autosomal dominant, or recessive pathogenic or likely pathogenic variants associated with psychiatric disorders in these two families. Nevertheless, we identified multiple rare inherited variants with unknown significance in the probands. In family 1, with singleton schizophrenia, we detected four rare variants in genes implicated in schizophrenia, including p.Arg1627Trp of LAMA2, p.Pro1338Ser of CSMD1, p.Arg691Gly of TLR4, and Arg182X of AGTR2. The p.Arg691Gly of TLR4 was inherited from the father, while the other three were inherited from the mother. In family 2, with two affected sisters diagnosed with major depressive disorder, we detected three rare variants shared by the two sisters in three genes implicated in affective disorders, including p.Ala4551Gly of FAT1, p.Val231Leu of HOMER3, and p.Ile185Met of GPM6B. These three rare variants were assumed to be inherited from their parents. Prompted by these findings, we suggest that these rare inherited variants may interact with each other and lead to psychiatric conditions in these two families. Our observations support the conclusion that inherited rare variants may contribute to the heritability of psychiatric disorders.

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“…A well-known CNV is the 22q11 deletion, 20-30% of people with it having SZ [79]. Additionally, There are many CNV Loci associated with SZ (Table 4) [80][81][82].…”

Section: Genetics and Epigenetics In Schizophreniamentioning

confidence: 99%

Neurobiological Perspective and Personalized Treatment in Schizophrenia

Tarhan¹,

Dılbaz²,

Shukurov³

et al. 2023

Schizophrenia - Recent Advances and Patient-Centered Treatment Perspectives

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Personalized treatment is the focus of researchers and comes into prominence for both genetic sciences and neurotechnology. Recently, clinical practice tries to follow the idea and principles of personalized medicine. Besides predicting an individual’s sensibility or predisposition for developing schizophrenia, pharmacogenetic and pharmacogenomic approaches attempt to define and acknowledge important indicators of clinical response to antipsychotics namely their efficacy and adverse effects. Particularly in the treatment of schizophrenia, clinicians are very helpless in resistant cases, and clinical pharmacogenomics contributes in a revolutionary way. With both phenotyping, namely Therapeutic Drug Monitoring (TDM) and genotyping, “big expectations” emerged both with the right drug, the right dose, and the right time. Both pharmacokinetic genotyping, CYP400 enzyme activity, and pharmacodynamic genotyping could be measured. The chapter handles schizophrenia with neurobiological views and covers personalized treatment approaches from various perspectives. Personalized treatment in the diagnosis and treatment of schizophrenia is presented first. Following comorbid schizophrenia in addition to the use of various substances, psychopharmacology of schizophrenia and the mechanism of action of antipsychotic drugs are presented. Genetics and epigenetics in schizophrenia are studied in detail and in silico application and computational approaches covering the feature extraction process and destructive impact of the metaverse are shared lastly.

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Chromosomal Microarray Analysis as First-Tier Genetic Test for Schizophrenia

Cited by 6 publications

References 91 publications

Exome sequencing as a first-tier test for copy number variant detection: retrospective evaluation and prospective screening in 2418 cases

Exome sequencing as a first-tier test for copy number variant detection: retrospective evaluation and prospective screening in 2418 cases

Whole Genome Sequencing Revealed Inherited Rare Oligogenic Variants Contributing to Schizophrenia and Major Depressive Disorder in Two Families

Neurobiological Perspective and Personalized Treatment in Schizophrenia

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