scholarly journals Comprehensive genome sequencing analyses identify novel gene mutations and copy number variations associated with infant developmental delay or intellectual disability (DD/ID)

2021 ◽  
Author(s):  
Yuxia Chen ◽  
Xiang Tang ◽  
Ling Liu ◽  
Qinrong Huang ◽  
Li Lin ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Genome Sequencing ◽  
Copy Number ◽  
Gene Mutations ◽  
Copy Number Variations ◽  
Novel Gene

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%).

Application of Restriction Site-Associated DNA Sequencing (RAD-Seq) for Copy Number Variation and Triploidy Detection in Human

2021 ◽  
pp. 1-8
Author(s):  
Jian-Chun He ◽  
Shao-Ying Li ◽  
Wen-Zhi He ◽  
Jia-Jia Xian ◽  
Xiao-Yan Ma ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
Cell Lines ◽  
Genome Sequencing ◽  
Copy Number ◽  
Restriction Site ◽  
Chromosomal Abnormalities ◽  
Copy Number Variations ◽  
Str Analysis ◽  
Tissue Samples ◽  
Low Pass

At present, low-pass whole-genome sequencing (WGS) is frequently used in clinical research and in the screening of copy number variations (CNVs). However, there are still some challenges in the detection of triploids. Restriction site-associated DNA sequencing (RAD-Seq) technology is a reduced-representation genome sequencing technology developed based on next-generation sequencing. Here, we verified whether RAD-Seq could be employed to detect CNVs and triploids. In this study, genomic DNA of 11 samples was extracted employing a routine method and used to build libraries. Five cell lines of known karyotypes and 6 triploid abortion tissue samples were included for RAD-Seq testing. The triploid samples were confirmed by STR analysis and also tested by low-pass WGS. The accuracy and efficiency of detecting CNVs and triploids by RAD-Seq were then assessed, compared with low-pass WGS. In our results, RAD-Seq detected 11 out of 11 (100%) chromosomal abnormalities, including 4 deletions and 1 aneuploidy in the purchased cell lines and all triploid samples. By contrast, these triploids were missed by low-pass WGS. Furthermore, RAD-Seq showed a higher resolution and more accurate allele frequency in the detection of triploids than low-pass WGS. Our study shows that, compared with low-pass WGS, RAD-Seq has relatively higher accuracy in CNV detection at a similar cost and is capable of identifying triploids. Therefore, the application of this technique in medical genetics has a significant potential value.

Genomic Syndromes in Schizophrenia

2013 ◽  
pp. 247-255
Author(s):  
George Kirov ◽  
Michael C. O’Donovan ◽  
Michael J. Owen
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Individual Risk ◽  
Genomic Deletions ◽  
Pathogenic Cnvs ◽  
Cognition And Learning

Several submicroscopic genomic deletions and duplications known as copy number variants (CNVs) have been reported to increase susceptibility to schizophrenia. Those for which the evidence is particularly strong include deletions at chromosomal segments 1q21.1, 3q29, 15q11.2, 15q13.3, 17q12 and 22q11.2, duplications at 15q11.2-q13.1, 16p13.1, and 16p11.2, and deletions atthe gene NRXN1. The effect of each on individual risk is relatively large, but it does not appear that any of them is alone sufficient to cause disorder in carriers. These CNVs often arise as new mutations(de novo). Analyses of genes enriched among schizophrenia implicated CNVs highlight the involvement in the disorder of post-synaptic processes relevant to glutamatergicsignalling, cognition and learning. CNVs that contribute to schizophrenia risk also contribute to other neurodevelopmental disorders, including intellectual disability, developmental delay and autism. As a result of selection, all known pathogenic CNVs are rare, and none makes a sizeable contribution to overall population risk of schizophrenia, although the study of these mutations is nevertheless providing important insights into the origins of the disorder.

scholarly journals A Case With 4 de Novo Copy Number Variations With Clinical Features That Overlap 1q43q44 Microdeletion and 3q29 Microduplication Syndromes

2018 ◽  
Vol 5 ◽  
pp. 2329048X1879820
Author(s):  
Miriam Kessi ◽  
Jing Peng ◽  
Lifen Yang ◽  
Haolin Duan ◽  
Yulin Tang ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Corpus Callosum ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variations ◽  
Language Delay ◽  
Global Developmental Delay ◽  
Recurrent Infections ◽  
Dental Anomalies ◽  
Microdeletion Syndrome

1q43q44 microdeletion syndrome is characterized by intellectual disability/global developmental delay, epilepsy, dysmorphic facies, stereotypic movement, language delay, recurrent infections, dental anomalies, and hand and foot anomalies. Microcephaly and corpus callosum dysplasia are present in some cases depending on gene content. 3q29 microduplication syndrome is characterized by intellectual disability, language delay, microcephaly, and dental anomalies. We report the first case with 4 de novo copy number variations with clinical features which overlap 1q43q44 microdeletion and 3q29 microduplication syndromes. Our case presented with global developmental delay, epilepsy, recurrent infections, stereotypic movements, speech delay, microcephaly, facial dysmorphism, bilateral clinodactyly, and small puffy feet with metatarsus varus; however, she had no corpus callosum dysplasia. Our case highlights the role of multiple copy number variations in the occurrence of a certain phenotype. Moreover, it supports the theory that the loss of HNRNPU gene function cannot explain the occurrence of microcephaly and abnormalities of the corpus callosum in 1q43q44 microdeletion syndrome.

scholarly journals Case Report: Temozolomide Treatment of Refractory Prolactinoma Resistant to Dopamine Agonists

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Tang ◽  
Yijun Cheng ◽  
Jinyan Huang ◽  
Jianfeng Li ◽  
Benyan Zhang ◽  
...  
Keyword(s):  
Complete Remission ◽  
Genome Sequencing ◽  
Copy Number ◽  
Dopamine Agonists ◽  
Tumor Volume ◽  
Gene Mutations ◽  
High Sensitivity ◽  
High Dose ◽  
Ki 67 ◽  
Continuous Increase

Therapeutic agents for refractory prolactinomas that are resistant to dopamine agonists (DAs) are troublesome, and surgery often only removes a large part of the tumor without complete remission. Among the various second-line treatment regimens, the treatment effect of the alkylating agent temozolomide (TMZ) is only effective for approximately half of patients; however, complete remission is rare. Here we report a patient with prolactinoma who was resistant to high-dose cabergoline (CAB) treatment, demonstrating a continuous increase in both the tumor volume and the prolactin (PRL) level. Given that this case is a refractory prolactinoma, the patient underwent two transsphenoidal approach (TSA) surgeries. The pathological analysis indicated that the Ki-67 index increased significantly from 3% to 30%, and the expression levels of DRD2 and MGMT were low. Finally, TMZ treatment was recommended. A total of six cycles of TMZ standard chemotherapy shrank the tumor volume and the tumor disappeared completely. During the 6-month follow-up period, the tumor did not relapse again, and the PRL level was also normal. RNA sequencing and DNA whole genome sequencing were performed on this prolactinoma specimen, revealing 16 possible gene mutations, including a missense mutation of the PABPC1 gene. Additionally, the copy number variation analysis results showed that several chromosomes had copy number gains compared to the matched peripheral blood sample. In this case, low expression of DRD2 and high proliferation led to resistance to CAB, whereas low MGMT expression contributed to sensitivity to TMZ treatment. The results of genome sequencing still need further investigation at the molecular level to explain the tumor aggressiveness and high sensitivity to TMZ.

scholarly journals Phenotypic and Molecular Cytogenetic Analysis of a Case of Monosomy 1p36 Syndrome due to Unbalanced Translocation

2020 ◽  
Vol 11 (5-6) ◽  
pp. 284-295
Author(s):  
Dalia F. Hussen ◽  
Alaa K. Kamel ◽  
Mona K. Mekkawy ◽  
Engy A. Ashaat ◽  
Mona O. El Ruby
Keyword(s):  
Intellectual Disability ◽  
Microarray Analysis ◽  
Cytogenetic Analysis ◽  
Copy Number ◽  
Clinical Manifestations ◽  
Copy Number Variations ◽  
Chromosomal Microarray Analysis ◽  
Fish Analysis ◽  
Unbalanced Translocation ◽  
Genotype Correlation

Monosomy 1p36 syndrome is one of the most common submicroscopic deletion syndromes, which is characterized by the presence of delayed developmental milestones, intellectual disability, and clinically recognizable dysmorphic craniofacial features. The syndrome comprises 4 cytogenetic groups including pure terminal deletions, interstitial deletions, complex rearrangements, and derivative chromosomes 1 due to unbalanced translocations, where unbalanced translocations represent the least percentage of all cases of monosomy 1p36 (7%). Most patients with monosomy 1p36 due to an unbalanced translocation can be cytogenetically diagnosed using conventional techniques. However, chromosomal microarray analysis is mandatory in these cases to detect copy number variance and size of the deletion and allows for setting a phenotype-genotype correlation. Here, we studied a 1.5-year-old female patient who showed intellectual disability, delayed milestones, hypotonia, seizures, and characteristic dysmorphic features including brachycephaly, straight eyebrows, deep-set eyes, downslanting palpebral fissures, midface hypoplasia, depressed nasal bridge, long philtrum, and pointed chin. Conventional cytogenetic analysis (CCA), microarray study, and fluorescence in situ hybridization (FISH) analysis were performed. CCA showed a translocation involving chromosomes 1 and 21, 45,XX,der(1)t(1;21)(p36.32;q21.1)dn. Microarray analysis revealed copy number losses at both 1p36 and proximal 21q. FISH confirmed the presence of the 1p36 deletion, but was not performed for 21q. We have concluded that phenotype-genotype correlation for monosomy 1p36 syndrome can be performed for the fundamental clinical manifestations; however, the final aspect of the syndrome depends on composite factors. Monosomy 1p36 due to unbalanced translocation may present either classically or with additional altered features of various severity based on the copy number variations involving different chromosomes.

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