scholarly journals Prenatal diagnosis of a 4.5-Mb deletion at chromosome 4q35.1q35.2: Case report and literature review

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Gefei Xiao ◽  
Xianrong Qiu ◽  
Yuqiu Zhou ◽  
Gongjun Tan ◽  
Yao Shen
Keyword(s):  
Single Copy ◽  
Peripheral Blood Lymphocytes ◽  
Chromosomal Microarray ◽  
Congenital Defects ◽  
Banding Technique ◽  
Chromosomal Microarray Analysis ◽  
Phenotype Correlation ◽  
Protein Coding ◽  
Genotype Phenotype Correlation ◽  
Number Variation

Abstract Objective We present a genetic analysis of an asymptomatic family with a 4q terminal deletion; we also review other similar published studies and discuss the genotype–phenotype correlation. Methods A karyotype analysis was performed on the amniotic fluid cells of a woman at 24 weeks of pregnancy and peripheral blood lymphocytes from both parents and their older son with the conventional G-banding technique. Chromosomal microarray analysis (CMA) testing was carried out for both parents and the fetus to analyze copy number variation (CNV) in the whole genome. Results The results showed no abnormalities in the karyotypes of the father and older son, and the karyotypes of the mother and fetus were 46,XX,del(4)(q35.1) and 46,XY,del(4)(q35.1), respectively. CMA results showed a partial deletion at the 4q terminus in both the fetus and mother. The deletion region of the fetus was arr[GRCh37] 4q35.1q35.2(186,431,008_190,957,460) × 1; the loss size of the CNV was approximately 4.5 Mb and involved 14 protein-coding genes, namely, CYP4V2, F11, FAM149A, FAT1, FRG1, FRG2, KLKB1, MTNR1A, PDLIM3, SORBS2, TLR3, TRIML1, TRIML2, and ZFP42. No variation on chromosome 4 was detected in the father’s CMA results. Conclusion Deletion of the 4q subtelomeric region is a familial variation. The arr[GRCh37] 4q35.1q35.2(186,431,008_190,957,460) region single-copy deletion did not cause obvious congenital defects or mental retardation. The application of high-resolution genetic testing technology combined with the analysis of public genetic database information can more clearly elucidate the genotype–phenotype correlation of the disease and provide support for both prenatal and postnatal genetic counseling.

scholarly journals Integrated CNV-seq, karyotyping and SNP-array analyses for effective prenatal diagnosis of chromosomal mosaicism

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Na Ma ◽  
Hui Xi ◽  
Jing Chen ◽  
Ying Peng ◽  
Zhengjun Jia ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Sex Chromosome ◽  
Snp Array ◽  
Genomic Rearrangements ◽  
Chromosomal Mosaicism ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Low Level ◽  
Autosomal Aneuploidy ◽  
Number Variation

Abstract Background Emerging studies suggest that low‐coverage massively parallel copy number variation sequencing (CNV-seq) more sensitive than chromosomal microarray analysis (CMA) for detecting low-level mosaicism. However, a retrospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of CNV-seq compared with CMA is warranted. Methods A total of 72 mosaicism cases identified by karyotyping or CMA were recruited to the study. There were 67 mosaic samples co-analysed by CMA and CNV-seq, comprising 40 with sex chromosome aneuploidy, 22 with autosomal aneuploidy and 5 with large cryptic genomic rearrangements. Results Of the 67 positive mosaic cases, the levels of mosaicism defined by CNV-seq ranged from 6 to 92% compared to the ratio from 3 to 90% by karyotyping and 20% to 72% by CMA. CNV-seq not only identified all 43 chromosomal aneuploidies or large cryptic genomic rearrangements detected by CMA, but also provided a 34.88% (15/43) increased yield compared with CMA. The improved yield of mosaicism detection by CNV-seq was largely due to the ability to detect low level mosaicism below 20%. Conclusion In the context of prenatal diagnosis, CNV-seq identified additional and clinically significant mosaicism with enhanced resolution and increased sensitivity. This study provides strong evidence for applying CNV-seq as an alternative to CMA for detection of aneuploidy and mosaic variants.

A case of deletion 8q22.2q22.3 in a child with de novo balanced translocation t(1;6)

2021 ◽  
pp. 49-56
Author(s):  
М.Е. Миньженкова ◽  
Ж.Г. Маркова ◽  
И.В. Анисимова ◽  
И.В. Канивец ◽  
Н.В. Шилова
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Current Trend ◽  
Chromosomal Microarray ◽  
Congenital Defects ◽  
Chromosomal Microarray Analysis ◽  
Balanced Translocation ◽  
Genomic Imbalance ◽  
Abnormal Phenotype ◽  
Balanced Translocations

Выяснение этиопатогенеза аномального фенотипа у пациентов со сбалансированными транслокациями является актуальным аспектом в современной клинической цитогенетике. Формирование аномалий развития может быть ассоциировано с наличием скрытого геномного дисбаланса как в точках разрывов, так и на хромосомах, не задействованных в перестройке. Целью данного исследования явилась этиологическая диагностика геномного дисбаланса у пациента со сбалансированной транслокацией и аномалиями развития. Для детекции геномного дисбаланса у пациента со сбалансированной транслокацией использовали хромосомный микроматричный анализ (ХМА) и FISH-исследование. У пациента со сбалансированной транслокацией при ХМА была выявлена делеция на хромосоме 8, не задействованной в транслокации. Таким образом, в статье представлен новый случай делеции 8q22.2q22.3 у пациента со сбалансированной транслокацией t(1;6) и аномалиями развития вследствие делеции. Identification of the etiopathogenesis of the abnormal phenotype in patients with balanced translocations is current trend in cytogenetic laboratories. The formation of developmental anomalies can be associated with the presence of a cryptic genomic imbalance both at breakpoints and on chromosomes not involved in rearrangements.The aim of this study is diagnostics of genomic imbalance in a patient with balanced translocation and abnormal phenotype. The case was characterized by GTG-banding, chromosomal microarray analysis and FISH diagnosis. We present a new case of deletion 8q22.2-q22.3 in child with balanced translocation t(1;6) and developmental delay/congenital defects due to deletion.

scholarly journals The Identification of Microdeletion and Reciprocal Microduplication in 22q11.2 Using High-Resolution CMA Technology

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ana Julia Cunha Leite ◽  
Irene Plaza Pinto ◽  
Damiana Mirian da Cruz e Cunha ◽  
Cristiano Luiz Ribeiro ◽  
Claudio Carlos da Silva ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Normal Karyotype ◽  
Clinical Indication ◽  
Deletion Syndrome ◽  
Chromosomal Microarray ◽  
Global Developmental Delay ◽  
Chromosomal Microarray Analysis ◽  
Genomic Deletions ◽  
Number Variation ◽  
Genomic Regions

The chromosome 22q11.2 region has long been implicated in genomic diseases. Some genomic regions exhibit numerous low copy repeats with high identity in which they provide increased genomic instability and mediate deletions and duplications in many disorders. DiGeorge Syndrome is the most common deletion syndrome and reciprocal duplications could be occurring in half of the frequency of microdeletions. We described five patients with phenotypic variability that carries deletions or reciprocal duplications at 22q11.2 detected by Chromosomal Microarray Analysis. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had clinical indication to global developmental delay and a normal karyotype. We observed in our study three microdeletions and two microduplications in 22q11.2 region with variable intervals containing known genes and unstudied transcripts as well as the LCRs that are often flanking and within this genomic rearrangement. The identification of these variants is of particular interest because it may provide insight into genes or genomic regions that are crucial for specific phenotypic manifestations and are useful to assist in the quest for understanding the mechanisms subjacent to genomic deletions and duplications.

scholarly journals Amplification, copy number variation, expression and association of non-synonymous SNP of bovine beta-defensin 129 gene with distinct fertility of cattle bull

2021 ◽  
Author(s):  
Subhash Solanki ◽  
Poonam Kashyap ◽  
Vijay Kumar ◽  
Martina Pukhrambam ◽  
Sachinandan De ◽  
...  
Keyword(s):  
Bovine Genome ◽  
Single Copy ◽  
Bioinformatic Analysis ◽  
Conception Rate ◽  
Polymorphism Analysis ◽  
Specific Class ◽  
Functional Protein ◽  
Protein Coding ◽  
Post Translational Modifications ◽  
Number Variation

Abstract Background: The male reproductive specific class-A β-defensins are adsorbed on sperm surface and enrich sperm functioning thus considered vital for maintaining male fertility. The primate DEFB129 play role in sperm maturation, motility, and fertilization but its contribution to bovine fertility is still unexplored.Method: RLM-RACE and RT-qPCR approaches were used to characterize and expression analysis of Indian cattle BBD129 gene. The polymorphism analysis of the BBD129 gene was done by PCR, sequencing, and absolute RT-qPCR on sperm gDNA from distinct fertility cattle bulls. Bioinformatic analysis was performed to understand the structural and functional implications of SNP on BBD129 protein.Results: The complete coding sequence of the BBD129 gene consists of 582 bp mRNA including UTRs and conserves all beta-defensin-like characteristics. Sequencing results revealed two conserved non-synonymous T169G (rs378737321, S57A) and A329G (rs383285978, N110S) SNPs in the functional protein-coding exon. Based on SNP position and linkage, BBD129 gene haplotypes were categorized into four groups: TA haplotype (169T & 329A), GA haplotype (T169G polymorphism), TG haplotype (A329G polymorphism), and GG haplotype (when T169G & A329G polymorphisms present together). The frequencies distributions of BBD129 haplotypes in the high fertile group (n=105 clones) were: TA (71.42%), GA (1.90%), TG (2.8%), and GG (24.76%), while in the low fertile group of bulls, the frequencies distributions of observed BBD129 haplotypes (n=149 clones) were: TA (36.24%), GA (0%), TG (2.68%), and GG (61.07%). The distributions of TA haplotype were majorly distributed in bulls with a high conception rate (P=0.5256) while double mutated GG haplotype was significantly more abundant in bulls with a lower conception rate (P=0.0001). BBD129 exist as a single-copy gene in the bovine genome and found higher expression in the corpus-epididymis region. Bioinformatic analyses found nsSNPs as neutral and non-deleterious but their structural-distorter could result in altered mRNA secondary structure, protein conformations decreased protein stability, and compromised biological functionalities. The polymorphisms resulted in altered O-glycosylations (deletion S57A and insertion N110S) and an increase in phosphorylations (52T-Threonine and 110S-Serine) post-translational-modifications.Conclusion: BBD129 gene polymorphism could be associated with the fertility performance of cattle bulls.

A Rare Case of Concomitant Deletions in 15q11.2 and 19p13.3

2018 ◽  
Vol 156 (2) ◽  
pp. 80-86
Author(s):  
Ilária C. Sgardioli ◽  
Elaine Lustosa-Mendes ◽  
Ana P. dos Santos ◽  
Társis P. Vieira ◽  
Vera L. Gil-da-Silva-Lopes
Keyword(s):  
Learning Difficulties ◽  
Velopharyngeal Insufficiency ◽  
Chromosomal Microarray ◽  
Imprinted Genes ◽  
Chromosomal Microarray Analysis ◽  
Phenotype Correlation ◽  
Behavioral Impairment ◽  
Motor Delay ◽  
15Q11.2 Deletion ◽  
Omim Database

A female individual with concomitant deletions in 15q11.2 and 19p13.3 is reported. She presents facial dysmorphisms, motor delay, learning difficulties, and mild behavioral impairment. After chromosomal microarray analysis, the final karyotype was established as 46,XX.arr[GRCh37] 15q11.2 (22770421_23282798)×1,19p13.3(3793904_4816330)×1. The deletion in 15q11.2 is 507 kb in size involving 7 non-imprinted genes, 4 of which are registered in the OMIM database and are implicated in neuropsychiatric or neurodevelopmental disorders. The deletion in 19p13.3 is 1,022 kb in size and encompasses 47 genes, most of which do not have a well-known function. The genotype-phenotype correlation is discussed, and most of the features could be related to the 19p13.3 deletion, except for velopharyngeal insufficiency. Other genes encompassed in the deleted region, as well as unrecognized epistatic factors could also be involved. Nevertheless, the two-hit model related to the 15q11.2 deletion would be an important hypothesis to be considered.

scholarly journals Molecular Characterization of Mosaicism for a Small Supernumerary Marker Chromosome Derived from Chromosome Y in an Infertile Male with Apparently Normal Phenotype: A Case Report and Literature Review

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Na An ◽  
Yang Yu ◽  
Qi Xi ◽  
Fagui Yue ◽  
Ruizhi Liu ◽  
...  
Keyword(s):  
Marker Chromosome ◽  
Normal Chromosome ◽  
Chromosomal Microarray ◽  
Banding Technique ◽  
Chromosomal Microarray Analysis ◽  
Infertile Male ◽  
Chromosome Y ◽  
Molecular Cytogenetic ◽  
Banding Analysis

Small supernumerary marker chromosomes (sSMCs), equal in size or smaller than chromosome 20 of the same metaphase, can hardly be identified through traditional banding technique. They are usually associated with intelligent disability, growth retardation, and infertility, but the genotype-phenotype correlations are still complicated for their complex origins and constitutions. Herein, we identified a 26-year-old Chinese infertile male who carried a mosaic sSMC and was diagnosed as severe oligospermia. The G-banding analysis initially described his karyotype as mos 47, XY, +mar[32]/46, XY[18]. The chromosomal microarray analysis results showed a 25.5 Mb gain in Yp11.31q11.23 and a 0.15 Mb loss in Yq12. Two SRY signals were discovered in the “seemingly” normal chromosome Y in both cell lines using SRY probe: one normal SRY was located on the distal tip of the short arm of chromosome Y while the other SRY was located on the terminal of long arm in the same chromosome Y. The sSMC(Y) was finally identified as der(Y) (pter ⟶ q11.23) (SRY-). To our knowledge, the chromosomal Y anomalies, SRY gene translocated from der(Y) (pter ⟶ q11.23) to qter of normal chromosome Y, were not reported before. Our findings indicated that the mosaic presence of sSMC(Y) may be the main cause of severe oligospermia although no other apparent abnormalities were observed in the proband. Further research on association between sSMC(Y) and spermatogenesis impairment should be investigated. It is recommended measures of traditional and molecular cytogenetic analysis should be taken to determine the origins and constitutions of sSMC so as to offer more appropriate genetic counseling for the infertile sSMC carriers.

Rapid Diagnosis of Imprinting Disorders Involving Copy Number Variation and Uniparental Disomy Using Genome-Wide SNP Microarrays

2015 ◽  
Vol 146 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Weiqiang Liu ◽  
Rui Zhang ◽  
Jun Wei ◽  
Huimin Zhang ◽  
Guojiu Yu ◽  
...  
Keyword(s):  
Copy Number ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Copy Number Variations ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Imprinting Disorders ◽  
Genome Wide ◽  
Number Variation ◽  
Efficient Alternative

Imprinting disorders, such as Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS) and Angelman syndrome (AS), can be detected via methylation analysis, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), or other methods. In this study, we applied single nucleotide polymorphism (SNP)-based chromosomal microarray analysis to detect copy number variations (CNVs) and uniparental disomy (UPD) events in patients with suspected imprinting disorders. Of 4 patients, 2 had a 5.25-Mb microdeletion in the 15q11.2q13.2 region, 1 had a 38.4-Mb mosaic UPD in the 11p15.4 region, and 1 had a 60-Mb detectable UPD between regions 14q13.2 and 14q32.13. Although the 14q32.2 region was classified as normal by SNP array for the 14q13 UPD patient, it turned out to be a heterodisomic UPD by short tandem repeat marker analysis. MS-MLPA analysis was performed to validate the variations. In conclusion, SNP-based microarray is an efficient alternative method for quickly and precisely diagnosing PWS, AS, BWS, and other imprinted gene-associated disorders when considering aberrations due to CNVs and most types of UPD.

A de novo 1q22q23.1 Interstitial Microdeletion in a Girl with Intellectual Disability and Multiple Congenital Anomalies Including Congenital Heart Defect

2018 ◽  
Vol 154 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Beata Aleksiūnienė ◽  
Egle Preiksaitiene ◽  
Aušra Morkūnienė ◽  
Laima Ambrozaitytė ◽  
Algirdas Utkus
Keyword(s):  
Intellectual Disability ◽  
Congenital Heart Defect ◽  
Congenital Heart ◽  
De Novo ◽  
Molecular Karyotyping ◽  
Pcr Analysis ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Protein Coding ◽  
Heart Defect

Many studies have shown that molecular karyotyping is an effective diagnostic tool in individuals with developmental delay/intellectual disability. We report on a de novo interstitial 1q22q23.1 microdeletion, 1.6 Mb in size, detected in a patient with short stature, microcephaly, hypoplastic corpus callosum, cleft palate, minor facial anomalies, congenital heart defect, camptodactyly of the 4-5th fingers, and intellectual disability. Chromosomal microarray analysis revealed a 1.6-Mb deletion in the 1q22q23.1 region, arr[GRCh37] 1q22q23.1(155630752_157193893)×1. Real-time PCR analysis confirmed its de novo origin. The deleted region encompasses 50 protein-coding genes, including the morbid genes APOA1BP, ARHGEF2, LAMTOR2, LMNA, NTRK1, PRCC, RIT1, SEMA4A, and YY1AP1. Although the unique phenotype observed in our patient can arise from the haploinsufficiency of the dosage-sensitive LMNA gene, the dosage imbalance of other genes implicated in the rearrangement could also contribute to the phenotype. Further studies are required for the delineation of the phenotype associated with this rare chromosomal alteration and elucidation of the critical genes for manifestation of the specific clinical features.

scholarly journals Deciphering the Invdupdel(8p) Genotype–Phenotype Correlation: Our Opinion

2020 ◽  
Vol 10 (7) ◽  
pp. 451
Author(s):  
Manuela Lo Bianco ◽  
Davide Vecchio ◽  
Tiziana A. Timpanaro ◽  
Alessia Arena ◽  
Marina Macchiaiolo ◽  
...  
Keyword(s):  
Chromosomal Rearrangement ◽  
Scientific Literature ◽  
De Novo ◽  
Congenital Defects ◽  
Phenotype Correlation ◽  
Intermediate Area ◽  
Neurodevelopmental Delay ◽  
Skeletal Malformations ◽  
Genotype Phenotype Correlation ◽  
Inverted Duplication

The 8p inverted duplication/deletion is a rare chromosomal rearrangement clinically featuring neurodevelopmental delay, mild to severe cognitive impairment, heart congenital defects and brain abnormalities. Patients affected also present typical facial dysmorphisms and skeletal malformations, and it is thought that the composite clinical picture may fall into the chromosomal rearrangement architecture. With the major aim of better framing its related clinical and diagnostic paths, we describe a patient carrying a de novo invdupde[8p] whose clinical features have not been described so far. Hence, through an extensive genotype–phenotype correlation analysis and by reviewing the dedicated scientific literature, we compared our patient’s features with those reported in other patients, which allows us to place our proband’s expressiveness in an intermediate area, widening the scope of the already known invdupde[8p] genotype–phenotype relationship.

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