scholarly journals CNTN6 copy number variations in 14 patients: a possible candidate gene for neurodevelopmental and neuropsychiatric disorders

2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Jie Hu ◽  
Jun Liao ◽  
Malini Sathanoori ◽  
Sally Kochmar ◽  
Jessica Sebastian ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Copy Number ◽  
Neuropsychiatric Disorders ◽  
Copy Number Variations

scholarly journals Copy Number Variations Analysis Identifies QPRT as a Candidate Gene Associated With Susceptibility for Solitary Functioning Kidney

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao Y. Zhou ◽  
Hao Y. Zheng ◽  
Li Han ◽  
Yan Wang ◽  
Li Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Candidate Gene ◽  
Copy Number ◽  
Copy Number Variations ◽  
Renal Tubules ◽  
Human Embryonic Kidney ◽  
Solitary Functioning Kidney ◽  
Triple X Syndrome ◽  
Pathogenic Cnvs ◽  
Functioning Kidney

BackgroundThe lack of understanding of molecular pathologies of the solitary functioning kidney makes improving and strengthening the continuity of care between pediatric and adult nephrological patients difficult. Copy number variations (CNVs) account for a molecular cause of solitary functioning kidney, but characterization of the pathogenic genes remains challenging.MethodsIn our prospective cohort study, 99 fetuses clinically diagnosed with a solitary functioning kidney were enrolled and evaluated using chromosomal microarray analysis (CMA). The genetic drivers for the pathogenic CNVs were analyzed. We characterized QPRT localization in fetal kidneys using immunohistochemistry and its expression in adult kidneys using quantitative RT-PCR. Further, QPRT was knocked down using siRNA in human embryonic kidney (HEK293T) cells, and the cell cycle and proliferation were tested.ResultsBesides one Triple X syndrome and one Down syndrome, we identified a total of 45 CNVs out of 34 subjects. Among the 14 pathogenic CNVs, CNV 16p11.2 reached the highest number of records with the phenotype of kidney anomalies in the Decipher database. Among the 26 genes within the 16p11.2 region, as a key enzyme for nicotinamide adenine dinucleotide (NAD+) biosynthesis, QPRT was distinctly localized in renal tubules but was barely observed in renal interstitial and glomeruli in fetal kidneys. The loss of QPRT prevented cells’ efficient transition into S phase, affected cell-cycle progression, and abrogated proliferation of human embryonic kidney cells.ConclusionOur data suggest that QPRT is a candidate gene associated with susceptibility for solitary functioning kidney. The CNVs discovered in our study exhibit great potential for future applications in genetic counseling and pregnancy management.

scholarly journals Detection of Clinically Relevant Copy Number Variations and Genes in a Bangladeshi Cohort of Neurodevelopmental Disorders

2021 ◽  
Author(s):  
Hosneara Akter ◽  
Muhammad Mizanur Rahman ◽  
Shaoli Sarker ◽  
Mohammed Basiruzzaman ◽  
Mazharul Islam ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
Critical Role ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Chromosomal Microarray Analysis ◽  
Potential Candidate ◽  
Female Ratio ◽  
Pathogenic Cnvs

Abstract Background: Copy number variations (CNVs) play a critical role into the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. Methods: We have conducted genome-wide chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare chromosomal abnormalities (deletion /duplication/ rearrangements). To identify candidate genes within the rare CNVs, multiple gene constraint metrics (i.e. “Critical-Exon Genes (CEGs)”) were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using R package. Results: In our cohort, the head circumference of males are significantly greater than females (p=0.0002). Of all samples assayed, 12.26% (26/212) and 47.17% (100/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. 2.83% (6/212) pathogenic CNVs are located at the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs in comparison to males (OR=4.2; p=0.0007). ADOS-2 subset show severe social communication deficit (p=0.014) and overall ASD symptoms severity (p=0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs and identified PSMC3 gene as a potential candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability. Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis therapeutics and management of NDD patients.

scholarly journals Dissecting Molecular Genetic Mechanisms of 1q21.1 CNV in Neuropsychiatric Disorders

2021 ◽  
Vol 22 (11) ◽  
pp. 5811
Author(s):  
Joy Yoon ◽  
Yingwei Mao
Keyword(s):  
Copy Number ◽  
Association Studies ◽  
Molecular Genetic ◽  
Neuropsychiatric Disorders ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Genetic Mechanisms

Pathogenic copy number variations (CNVs) contribute to the etiology of neurodevelopmental/neuropsychiatric disorders (NDs). Increased CNV burden has been found to be critically involved in NDs compared with controls in clinical studies. The 1q21.1 CNVs, rare and large chromosomal microduplications and microdeletions, are detected in many patients with NDs. Phenotypes of duplication and deletion appear at the two ends of the spectrum. Microdeletions are predominant in individuals with schizophrenia (SCZ) and microcephaly, whereas microduplications are predominant in individuals with autism spectrum disorder (ASD) and macrocephaly. However, its complexity hinders the discovery of molecular pathways and phenotypic networks. In this review, we summarize the recent genome-wide association studies (GWASs) that have identified candidate genes positively correlated with 1q21.1 CNVs, which are likely to contribute to abnormal phenotypes in carriers. We discuss the clinical data implicated in the 1q21.1 genetic structure that is strongly associated with neurodevelopmental dysfunctions like cognitive impairment and reduced synaptic plasticity. We further present variations reported in the phenotypic severity, genomic penetrance and inheritance.

X-linked CNV and skewed X-chromosome inactivation

2020 ◽  
pp. 19-21
Author(s):  
Е.А. Фонова ◽  
Е.Н. Толмачева ◽  
А.А. Кашеварова ◽  
М.Е. Лопаткина ◽  
К.А. Павлова ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Intellectual Disability ◽  
X Chromosome ◽  
Copy Number ◽  
Copy Number Variations ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromosome X ◽  
Skewed X Chromosome Inactivation

Смещение инактивации Х-хромосомы может быть следствием и маркером нарушения клеточной пролиферации при вариациях числа копий ДНК на Х-хромосоме. Х-сцепленные CNV выявляются как у женщин с невынашиванием беременности и смещением инактивации Х-хромосомы (с частотой 33,3%), так и у пациентов с умственной отсталостью и смещением инактивацией у их матерей (с частотой 40%). A skewed X-chromosome inactivation can be a consequence and a marker of impaired cell proliferation in the presence of copy number variations (CNV) on the X chromosome. X-linked CNVs are detected in women with miscarriages and a skewed X-chromosome inactivation (with a frequency of 33.3%), as well as in patients with intellectual disability and skewed X-chromosome inactivation in their mothers (with a frequency of 40%).

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