Large Duplications Can Be Benign Copy Number Variants: A Case of a 3.6-Mb Xq21.33 Duplication

2017 ◽  
Vol 151 (3) ◽  
pp. 115-118 ◽  
Author(s):  
Marie-Laure Maurin ◽  
Chloé Arfeuille ◽  
Pascale Sonigo ◽  
Sophie Rondeau ◽  
Michel Vekemans ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Gene Density ◽  
Phenotypic Effect ◽  
Female Fetus ◽  
Genomic Imbalances ◽  
Clinical Consequences ◽  
Male Patients ◽  
Preferential Inactivation ◽  
Female Carriers

Segmental aneusomies are usually associated with clinical consequences, but an increasing number of nonpathogenic cytogenetically visible as well as large cryptic chromosomal imbalances have been reported. Here, we report a 3.6-Mb Xq21.33 microduplication detected prenatally on a female fetus which was inherited from a phenotypically normal mother and grandfather. It is assumed that male patients harboring Xq or Xp duplication present with syndromic intellectual disability because of functional disomy of the corresponding genes. Female carriers are generally asymptomatic because of preferential inactivation of the abnormal X. In the present case, the 3.6-Mb-duplicated segment encompasses only 2 genes, DIAPH2 and RPL4A. Since the asymptomatic grandfather carries the duplication, we hypothesize that these genes are not dosage sensitive and/or involved in cognitive function. Our observation further illustrates that large copy number variants can be associated with a normal phenotype, especially where gene density is low. Reporting rare cases of large genomic imbalances without a phenotypic effect can be very helpful, especially for genetic counseling in the prenatal setting.

scholarly journals Functional and clinical consequences of Fc receptor polymorphic and copy number variants

2009 ◽  
Vol 157 (2) ◽  
pp. 244-254 ◽  
Author(s):  
S. Bournazos ◽  
J. M. Woof ◽  
S. P. Hart ◽  
I. Dransfield
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Fc Receptor ◽  
Clinical Consequences

scholarly journals Recurrent Copy Number Variants Associated with Syndromic Short Stature of Unknown Cause

2017 ◽  
Vol 89 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Thais K. Homma ◽  
Ana C.V. Krepischi ◽  
Tatiane K. Furuya ◽  
Rachel S. Honjo ◽  
Alexsandra C. Malaquias ◽  
...  
Keyword(s):  
Short Stature ◽  
Copy Number ◽  
Single Nucleotide Polymorphism Array ◽  
Copy Number Variants ◽  
Chromosomal Microarray ◽  
Unknown Etiology ◽  
Comparative Genomic ◽  
Growth Disorders ◽  
Genomic Imbalances ◽  
Pathogenic Cnvs

Background/Aims: Genetic imbalances are responsible for many cases of short stature of unknown etiology. This study aims to identify recurrent pathogenic copy number variants (CNVs) in patients with syndromic short stature of unknown cause. Methods: We selected 229 children with short stature and dysmorphic features, developmental delay, and/or intellectual disability, but without a recognized syndrome. All patients were evaluated by chromosomal microarray (array-based comparative genomic hybridization/single nucleotide polymorphism array). Additionally, we searched databases and previous studies to recover recurrent pathogenic CNVs associated with short stature. Results: We identified 32 pathogenic/probably pathogenic CNVs in 229 patients. By reviewing the literature, we selected 4 previous studies which evaluated CNVs in cohorts of patients with short stature. Taken together, there were 671 patients with short stature of unknown cause evaluated by chromosomal microarray. Pathogenic/probably pathogenic CNVs were identified in 87 patients (13%). Seven recurrent CNVs, 22q11.21, 15q26, 1p36.33, Xp22.33, 17p13.3, 1q21.1, 2q24.2, were observed. They are responsible for about 40% of all pathogenic/probably pathogenic genomic imbalances found in short stature patients of unknown cause. Conclusion: CNVs seem to play a significant role in patients with short stature. Chromosomal microarray should be used as a diagnostic tool for evaluation of growth disorders, especially for syndromic short stature of unknown cause.

Sporadic male patients with intellectual disability: Contribution of X-chromosome copy number variants

2012 ◽  
Vol 55 (11) ◽  
pp. 577-585 ◽  
Author(s):  
M. Isrie ◽  
G. Froyen ◽  
K. Devriendt ◽  
T. de Ravel ◽  
J.P. Fryns ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
X Chromosome ◽  
Copy Number ◽  
Copy Number Variants ◽  
Chromosome Copy Number ◽  
Male Patients

scholarly journals Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency

2020 ◽  
Vol 21 (16) ◽  
pp. 5757
Author(s):  
Bartłomiej Budny ◽  
Katarzyna Karmelita-Katulska ◽  
Marek Stajgis ◽  
Tomasz Żemojtel ◽  
Marek Ruchała ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variants ◽  
Copy Number Variations ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency ◽  
Functional Studies ◽  
Genomic Imbalances ◽  
Whole Exome

Combined pituitary hormone deficiency represents a disorder with complex etiology. For many patients, causes of the disease remain unexplained, despite usage of advanced genetic testing. Although major and common transcription factors were identified two decades ago, we still struggle with identification of rare inborn factors contributing to pituitary function. In this report, we follow up genomic screening of CPHD patient cohort that were previously tested for changes in a coding sequences of genes with the use of the whole exome. We aimed to find contribution of rare copy number variations (CNVs). As a result, we identified genomic imbalances in 7 regions among 12 CPHD patients. Five out of seven regions showed copy gains whereas two presented losses of genomic fragment. Three regions with detected gains encompassed known CPHD genes namely LHX4, HESX1, and OTX2. Among new CPHD loci, the most interesting seem to be the region covering SIX3 gene, that is abundantly expressed in developing brain, and together with HESX1 contributes to pituitary organogenesis as it was evidenced before in functional studies. In conclusion, with the use of broadened genomic approach we identified copy number imbalances for 12 CPHD patients. Although further functional studies are required in order to estimate its true impact on expression pattern during pituitary organogenesis and CPHD etiology.

Understanding Schizophrenia: Genetic Causes and Treatment

2019 ◽  
Vol 1 (1) ◽  
pp. 6-12
Author(s):  
Fatima Javeria ◽  
Shazma Altaf ◽  
Alishah Zair ◽  
Rana Khalid Iqbal
Keyword(s):  
Copy Number ◽  
Drug Targets ◽  
Disease Risk ◽  
Mental Disease ◽  
Copy Number Variants ◽  
Aminobutyric Acid ◽  
Epigenetic Mechanisms ◽  
Gamma Aminobutyric Acid ◽  
Wide Range ◽  
Severe Mental Disease

Schizophrenia is a severe mental disease. The word schizophrenia literally means split mind. There are three major categories of symptoms which include positive, negative and cognitive symptoms. The disease is characterized by symptoms of hallucination, delusions, disorganized thinking and speech. Schizophrenia is related to many other mental and psychological problems like suicide, depression, hallucinations. Including these, it is also a problem for the patient’s family and the caregiver. There is no clear reason for the disease, but with the advances in molecular genetics; certain epigenetic mechanisms are involved in the pathophysiology of the disease. Epigenetic mechanisms that are mainly involved are the DNA methylation, copy number variants. With the advent of GWAS, a wide range of SNPs is found linked with the etiology of schizophrenia. These SNPs serve as ‘hubs’; because these all are integrating with each other in causing of schizophrenia risk. Until recently, there is no treatment available to cure the disease; but anti-psychotics can reduce the disease risk by minimizing its symptoms. Dopamine, serotonin, gamma-aminobutyric acid, are the neurotransmitters which serve as drug targets in the treatment of schizophrenia. Due to the involvement of genetic and epigenetic mechanisms, drugs available are already targeting certain genes involved in the etiology of the disease.

Koduojančios ir nekoduojančios genomo sekos variantų bei kopijų skaičiaus pokyčių molekulinis ir funkcinis vertinimas

2020 ◽  
Author(s):  
◽  
Evelina Siavrienė
Keyword(s):  
Genome Sequence ◽  
Copy Number ◽  
Copy Number Variants ◽  
Sequence Variants ◽  
Functional Evaluation

A Molecular and Functional Evaluation of Coding and Non-Coding Genome Sequence Variants and Copy Number Variants

0306 Exploring the feasibility of using copy number variants as genetic markers through large-scale whole genome sequencing experiments

2016 ◽  
Vol 94 (suppl_5) ◽  
pp. 146-146
Author(s):  
D. M. Bickhart ◽  
L. Xu ◽  
J. L. Hutchison ◽  
J. B. Cole ◽  
D. J. Null ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genetic Markers ◽  
Genome Sequencing ◽  
Copy Number ◽  
Large Scale ◽  
Copy Number Variants ◽  
Whole Genome
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