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1.
Braz. j. biol ; 84: e250575, 2024. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1350309

ABSTRACT

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.


Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.


Subject(s)
Humans , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Liver Neoplasms , Prognosis , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Up-Regulation , DNA-Binding Proteins , DNA Copy Number Variations
2.
Biomédica (Bogotá) ; 41(2): 282-292, abr.-jun. 2021. tab, graf
Article in Spanish | LILACS | ID: biblio-1339267

ABSTRACT

Resumen | Introducción. Las aneuploidías son trastornos genéticos frecuentes en la práctica clínica; sin embargo, se conoce poco sobre las otras variantes genéticas que modifican el fenotipo final. Objetivo. Determinar las variantes en el número de copias y las regiones con pérdida de heterocigosidad autosómica mayor de 0,5 % o de regiones mayores de 10 Mb en neonatos con aneuploidías autosómicas. Materiales y métodos. Se hizo el análisis cromosómico por micromatrices a los neonatos con aneuploidías autosómicas (n=7), trisomía 21 (n=5) y trisomía 18 (n=2) evaluados en los hospitales Antonio Lorena y Regional de Cusco, Perú, en el 2018. Resultados. En dos neonatos se encontraron variantes en el número de copias, patogénicas o probablemente patogénicas, en regiones diferentes al cromosoma 21 o al 18. Además, se observaron dos variantes del número de copias con más de 500 kpb de patogenia desconocida. Conclusiones. Si bien el número de pacientes era muy reducido, es importante resaltar que se encontraron otras variantes en el número de copias que se han descrito asociadas con trastornos del neurodesarrollo, varias anomalías congénitas, hipoacusia y talla baja o alta, entre otras, lo que probablemente influye negativamente en el fenotipo de este grupo de pacientes.


Abstract | Introduction: Aneuploidies are frequent genetic disorders in clinical practice. However, little is known about other genetic variants that may influence the final phenotype. Objective: To determine the variations in the number of copies and regions with homozygosity greater than 0.5% or larger than 10 Mb in newborns with autosomal aneuploidies. Materials and methods: We performed a chromosomal microarray analysis on newborns with autosomal aneuploidies (n=7), trisomy 21 (n=5), and trisomy 18 (n=2) evaluated at the Hospital Antonio Lorena and Hospital Regional of Cusco, Perú, during 2018. Results: We found pathogenic and probably pathogenic variants in the number of copies in other genomic regions different to chromosomes 21 or 18 in two neonates. Additionally, we found two variants bigger than 500 kpb of unknown pathogenicity. Conclusions: Although the number of analyzed individuals was small, it is important to highlight that we found other variants in the number of copies that have been described in association with neurodevelopmental disorders, congenital anomalies, deafness, and short/ tall stature, among others, in almost half of them, which will probably impact the phenotype negatively in patients with aneuploidies.


Subject(s)
DNA Copy Number Variations , Aneuploidy , Infant, Newborn , Deafness , Neurodevelopmental Disorders
3.
Article in Chinese | WPRIM | ID: wpr-888398

ABSTRACT

OBJECTIVE@#To investigate the association of fetal cardiac structural abnormalities with chromosomal aneuploidies and copy number variations (CNVs) in amniocytes.@*METHODS@#328 pregnant women were subjected to fetal ultrasonography and chromosomal microarray analysis (CMA). Based on the fetal heart structure, the subjects were divided into normal (n=273) and abnormal groups (n=55). The detection rates of chromosomal aneuploidies and CNVs were compared between the two groups. Spearman method was used to assess the association between the results and fetal cardiac structural abnormalities.@*RESULTS@#The detection rates for chromosomal aneuploidies and CNVs in the abnormal group were significantly higher than that in the normal group (P< 0.05), and the incidence of fetal cardiac structural abnormalities was strongly associated with chromosomal aneuploidies and CNVs (P< 0.05).@*CONCLUSION@#Fetal chromosomal aneuploidies and CNVs are strongly associated with cardiac structural abnormalities.


Subject(s)
Aneuploidy , Chromosome Aberrations , DNA Copy Number Variations , Female , Fetus , Humans , Microarray Analysis , Pregnancy , Prenatal Diagnosis , Ultrasonography, Prenatal
4.
Article in Chinese | WPRIM | ID: wpr-888387

ABSTRACT

OBJECTIVE@#Clinical examination and molecular genetic analysis were carried out for one case with special facial features with developmental retardation, hearing impairment and cleft lip and palate.@*METHODS@#The intelligence test, hearing test, and MRI test were performed. At the same time, the blood were collected to detect the copy number variation of the whole genome with the chromosomal karyotype analysis and the chromosomal microarray analysis (CMA). And the whole exome sequencing (WES) was used to analyze the pathogenic variant.@*RESULTS@#The children had mild mental retardation and the IQ was 61. There was moderate hearing loss in both ears(left ear 60 dB, right ear 65 dB). And bilateral horizontal hypoplasia of semicircular canal was found by cranial MRI test. No copy number abnormality was found by chromosome karyotype analysis and chromosome microarray analysis in peripheral blood. And whole exome sequencing suggested that there was heterozygous pathogenic variants in KMT2D gene (p.Leu545Argfs*385).@*CONCLUSION@#The patient has a peculiar face and multiple system defects, and was diagnosed as Niikawa-Kuroki syndrome type I by KMT2D gene variant. The whole exome sequencing is helpful for the diagnosis of complex genetic diseases.


Subject(s)
Abnormalities, Multiple , Child , Cleft Lip , Cleft Palate , DNA Copy Number Variations , Face/abnormalities , Hematologic Diseases , Humans , Vestibular Diseases
5.
Article in Chinese | WPRIM | ID: wpr-888380

ABSTRACT

OBJECTIVE@#To explore the genetic etiology for a Chinese pedigree affected with Angelman syndrome (AS).@*METHODS@#The proband with phenotypes suggestive of AS was subjected to copy number variation sequencing (CNV-seq), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and high-throughput next generation sequencing (NGS). Variant of the UBE3A gene was verified among family members by Sanger sequencing and bioinformatic analysis.@*RESULTS@#NGS revealed that the proband has carried a heterozygous variant of the UBE3A gene, namely c.1517G>A (p.R506H). The variant has co-segregated with the disease in the pedigree. Multiple amino acid sequence alignment showed that the site of mutant residue is conserved among nine homologous species. The variant was predicted to be deleterious by bioinformatic analysis.@*CONCLUSION@#A novel variant of the UBE3A gene has been identified in a Chinese pedigree affected with AS. Above finding has further expanded the spectrum of UBE3A gene variants and phenotypes of AS, which also facilitated molecular diagnosis and genetic counseling for the family.


Subject(s)
Angelman Syndrome/genetics , China , DNA Copy Number Variations , Humans , Mutation , Pedigree , Phenotype
6.
Article in Chinese | WPRIM | ID: wpr-888369

ABSTRACT

OBJECTIVE@#To analyze the prenatal diagnosis, parental verification and pregnancy outcome of 6 fetuses with 22q11.2 microdeletion syndrome.@*METHODS@#Copy number variation sequencing (CNV-seq)and chromosomal microarray analysis (CMA) were carried out for the fetuses.@*RESULTS@#The fetuses were found to harbor 2.54-3.2 Mb microdeletions of the 22q11.2 region, among which one was maternally inherited and one was paternally inherited. Two parents opted to continue with the pregnancy, and 4 chose induced labor. One fetus was found to have tetralogy of Fallot, while two carrier parents and one fetus appeared to have normal phenotype.@*CONCLUSION@#22q11.2 microdeletions identified upon prenatal diagnosis should be treated carefully, with ultrasonic scan and parental verification taken into account.


Subject(s)
DNA Copy Number Variations , Female , Fetus , Humans , Microarray Analysis , Pregnancy , Pregnancy Outcome , Prenatal Diagnosis , Ultrasonography, Prenatal
7.
Article in Chinese | WPRIM | ID: wpr-888366

ABSTRACT

OBJECTIVE@#To explore the genetic etiology for a fetus with congenital orofacial cleft.@*METHODS@#Single nucleotide polymorphism microarray (SNP array) was carried out on skin tissues sampled from the fetus following induced abortion for the detection of copy number variation (CNVs). Pathogenicity of the candidate gene was validated through experiment.@*RESULTS@#SNP array revealed that the fetus has carried a hemizygous 9.23Mb deletion at Xq21.31-q22.1(91 063 807-100 293 555), which was inherited from its mother. The region contained 13 OMIM genes and 1 ncRNA coding gene(MIR548M). Inhibiting of the expression of the MIR548M gene in oral epithelial celllines has resulted in up-regulation of the expression of SUMO1 gene which was known to involve in the pathogenesis of orofacial cleft.@*CONCLUSION@#Dosage insufficiency of the MIR548M gene may underlie the etiology of orofacial cleft in this fetus.


Subject(s)
Cleft Lip/genetics , Cleft Palate/genetics , DNA Copy Number Variations/genetics , Female , Fetus , Humans , MicroRNAs/genetics , Polymorphism, Single Nucleotide , Pregnancy , SUMO-1 Protein
8.
Article in Chinese | WPRIM | ID: wpr-888359

ABSTRACT

Genomic disorders caused by pathogenic copy number variation (pCNV) have proven to underlie a significant proportion of birth defects. With technological advance, improvement of bioinformatics analysis procedure, and accumulation of clinical data, non-invasive prenatal screening of pCNV (NIPS-pCNV) by high-throughput sequencing of maternal plasma cell-free DNA has been put to use in clinical settings. Specialized standards for clinical application of NIPS-pCNV are required. Based on the discussion, 10 pCNV-associated diseases with well-defined conditions and 5 common chromosomal aneuploidy syndromes are recommended as the target of screening in this consensus. Meanwhile, a standardized procedure for NIPS-pCNV is also provided, which may facilitate propagation of this technique in clinical settings.


Subject(s)
Aneuploidy , Cell-Free Nucleic Acids/genetics , Consensus , DNA Copy Number Variations , Female , High-Throughput Nucleotide Sequencing , Humans , Pregnancy , Prenatal Diagnosis
9.
Journal of Experimental Hematology ; (6): 1785-1789, 2021.
Article in Chinese | WPRIM | ID: wpr-922335

ABSTRACT

OBJECTIVE@#To investigate the effect of EBV-DNA copy number on the prognosis of patients with EBV positive lymphoma.@*METHODS@#Clinical data of 109 patients diagnosed as EBV positive lymphoma in Tianjin Medical University Cancer Institute and Hospital from January 2010 to January 2020 were enrolled and analyzed retrospectively. Kaplan-Meier analysis was used for survival analysis, Log-rank was used to compare the clinical characteristics between the patients in different groups, and Cox regression was used for multivariate analysis.@*RESULTS@#Among the 109 patients with EBV-positive lymphoma, the medium age were 56 (range 15 to 83) years old. 29 patients at Ann Arbor stage I-II while 80 patients at stage III-IV. The average value of EBV-DNA was 1 023 510 IU/ml, 7 patients were higher than the average value, while 102 patients were lower. KM survival analysis showed that OS and PFS in patients with EBV-DNA above average level were shorter than those in patients with EBV-DNA below average level (OS: P=0.048, PFS: P=0.001), EBV-DNA copy number was a factor affecting the prognosis of patients. In addition, LDH level showed positive correlation with EBV-DNA copy number (r=0.650), which was also one of the factors affecting OS (P=0.053).@*CONCLUSION@#EBV-DNA copy number and LDH level can influence the prognosis of EBV positive lymphoma patients. Therefore, detection of EBV-DNA copy number in peripheral blood is important for evaluate the prognosis the patients.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , DNA Copy Number Variations , DNA, Viral , Herpesvirus 4, Human , Humans , Lymphoma , Middle Aged , Retrospective Studies , Young Adult
10.
Article in Chinese | WPRIM | ID: wpr-922036

ABSTRACT

OBJECTIVE@#To assess the correlation of borderline fetal ventriculomegaly with genomic copy number variations (CNVs) and outcome of pregnancy.@*METHODS@#For 84 singleton pregnancies diagnosed with VM, chromosomal microarray analysis (CMA) was carried out to detect the CNVs of the fetal genome. Outcome of the pregnancy and neonatal development were analyzed. The pregnant women were divided into mild group (10-12 mm), moderate group (12-15 mm) and severe group (>= 15 mm) based on the severity of fetal ventriculomegaly. The detection rate of pathogenic CNVs and pregnancy outcome were compared. Multivariate logistic regression was carried out to analyze the predictors for pregnancy outcome.@*RESULTS@#Respectively, 24, 28 and 32 fetuses were assigned into the mild, moderate and severe groups. CMA has detected 15 cases of chromosomal abnormalities, including 11 pathogenic CNVs and 4 abnormal karyotypes. Abnormal pregnancy outcomes were found in 20 fetuses, including 12 with hydrocephalus and 8 with chromosomal microdeletion syndromes. A significant difference was found in the detection rate of fetal pathogenic CNVs and abnormal pregnancy outcome among the three groups (P<0.05). Multivariate logistic regression analysis showed that the largest change of lateral ventricle width (OR = 1.868, 95%CI = 1.120-3.116) and the extent of lateral ventricle widening (OR = 1.571, 95%CI = 1.120-2.206) were the key factors affecting the outcome of pregnancy (P<0.05).@*CONCLUSION@#Borderline fetal VM is associated with the risk of pathogenic CNVs and adverse pregnancy outcome. A comprehensive examination is required after prenatal ultrasound diagnosis, which is conducive to prenatal consultation and prognostic evaluation of the fetus.


Subject(s)
Chromosome Aberrations , DNA Copy Number Variations , Female , Fetus , Humans , Hydrocephalus/genetics , Infant, Newborn , Microarray Analysis , Pregnancy , Pregnancy Outcome , Prenatal Diagnosis
11.
Article in Chinese | WPRIM | ID: wpr-922033

ABSTRACT

OBJECTIVE@#To provide genetic counseling for a couple with recurrent detection of fetal structural abnormality during second trimester pregnancy.@*METHODS@#The fetal tissue and peripheral blood samples of the couple were subjected to G banded chromosomal analysis, copy number variation sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) assays.@*RESULTS@#CNV-seq has detected a 6.59 Mb duplication at 7p22.3-p22.1 and a 3.81 Mb deletion at 4p16.3 in the fetal tissue, though conventional karyotyping results of both parents were normal. FISH has confirmed that the father has harbored a cryptic translocation of t(4;7)(7p+,4q+,4p+,7q+).@*CONCLUSION@#The ultrasonographic abnormality of the fetuses may be attributed to the 7p microduplication and 4p microdeletion derived from the cryptic translocation carried by the father. Reciprocal translocation of tiny chromosomal segments should be suspected for couples with recurrent adverse pregnancies but apparently normal karyotypes.


Subject(s)
Chromosome Disorders , DNA Copy Number Variations , Female , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Pregnancy , Translocation, Genetic
12.
Article in Chinese | WPRIM | ID: wpr-922025

ABSTRACT

OBJECTIVE@#To analyze the molecular genetics of a Chinese pedigree with congenital hand foot cleft.@*METHODS@#Single nucleotide polymorphism microarray (SNP array) was used to analyze the whole genome copy number variation.@*RESULTS@#SNP array analysis showed that there was a 433 kb repeat in 10q24.31-10q24.32 region, which contained LBX1, BTRC, POLL, OPCD and FBXW4 genes.@*CONCLUSION@#Microduplication of chromosome 10q24.31-10q24.32 may be the cause of congenital hand foot cleft in this pedigree.


Subject(s)
China , DNA Copy Number Variations/genetics , Foot Deformities, Congenital/genetics , Hand Deformities, Congenital/genetics , Humans , Pedigree
13.
Article in Chinese | WPRIM | ID: wpr-922021

ABSTRACT

OBJECTIVE@#To analyze the clinical symptom and parental origin of patients with MECP2 duplication syndrome in order to provide a basis for genetic counseling and prenatal diagnosis.@*METHODS@#Clinical symptoms of four patients who were diagnosed with MECP2 duplication syndrome by copy number variation sequencing (CNV-Seq) were reviewed. The maternal origin of the duplications were verified.@*RESULTS@#All patients were males, and CNV-Seq revealed that they have all harbored a duplication in the Xq28 region spanning 0.32 ~ 0.86 Mb, which were derived from asymptomatic mothers. The clinical symptoms of three patients with three copies included delayed speech, intellectual disability, and muscular hypotonia, while the patient with four copies had died at 6 months after birth, with clinical symptoms including recurrent infections, seizures, and spasticity.@*CONCLUSION@#The four cases of MECP2 duplication syndrome have shown complete penetrance and have all derived from asymptomatic mothers. As a stable and reliable method, CNV-Seq can accurately detect the MECP2 duplication syndrome.


Subject(s)
Chromosomes, Human, X , DNA Copy Number Variations , Gene Duplication , Humans , Male , Mental Retardation, X-Linked , Methyl-CpG-Binding Protein 2/genetics , Phenotype
14.
Article in Chinese | WPRIM | ID: wpr-922013

ABSTRACT

OBJECTIVE@#To explore the genetic etiology of a neonate with suggestive features of Cornelia de Lange Syndrome (CdLS).@*METHODS@#Chromosome karyotyping, copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the child. Meanwhile, peripheral venous blood samples were taken from his parents for verifying the suspected pathogenic variants detected in the child.@*RESULTS@#The child has exhibited developmental delay, microcephaly, ptosis, micrognathia, and low ear setting, and was suspected as CdLS. No abnormality was found by karyotyping and CNV-seq analysis. WES has detected 5 heterogeneous variants and 1 hemizygous variant on the X chromosome. Combining the genetic pattern and result of family verification, a hemizygous C.3500T>C (p.ile1167thr) of the SMC1A gene was predicted to underlay the clinical manifestations of the patient. This variant was not recorded in the dbSNP and gnomAD database. PolyPhen2, Provean, SIFT all predicted the variant to be harmful, and PhastCons conservative prediction is was a conservative mutation. ACMG variant classification standard evidence supports are PM2, PP2, and PP3.@*CONCLUSION@#The novel c.3500T>C (p.Ile1167Thr) missense mutation of the SMC1A gene probably underlay the genetic etiology of CdLS in this child. Above results has enriched the mutation spectrum of CdLS type II, and facilitated clinical counseling for this family.


Subject(s)
Cell Cycle Proteins/genetics , Child , DNA Copy Number Variations , De Lange Syndrome/genetics , Humans , Infant, Newborn , Mutation , Phenotype , Whole Exome Sequencing
15.
Article in Chinese | WPRIM | ID: wpr-922012

ABSTRACT

OBJECTIVE@#To explore the clinical features and genetic characteristics of a child with 5q14.3 microdeletion syndrome.@*METHODS@#Whole exome sequencing (WES) and low-coverage massively parallel copy number variation sequencing (CNV-seq) were used to determine the potentially pathogenic variants as well as the copy number variations (CNVs). Candidate CNVs were verified by real-time fluorescence quantitative PCR.@*RESULTS@#The patient presented with psychomotor retardation, epilepsy, peculiar face and hypotonia. The results of WES suggested that he has carried a heterozygous deletion for chr5:86 564 268-88 119 605. CNV-seq indicated that the patient carried a heterozygous deletion of 4.76 Mb heterozygous deletion on chromosome 5q14.3. The MEF2C gene and RASA1 gene in the deletion area were verified by real-time fluorescence quantitative PCR. The results showed that the MEF2C geneand RASA1 gene were heterozygous deletion, which was consistent with the sequencing results.@*CONCLUSION@#The child was diagnosed with 5q14.3 microdeletion syndrome. Haploinsufficiency of the MEF2C gene may underlie the manifestations of 5q14.3 microdeletion syndrome.


Subject(s)
Chromosome Deletion , Chromosome Disorders , DNA Copy Number Variations , Genetic Testing , Humans , Male , Phenotype , Whole Exome Sequencing , p120 GTPase Activating Protein
16.
Article in Chinese | WPRIM | ID: wpr-921998

ABSTRACT

OBJECTIVE@#To investigate the ultrasonographic findings and genetic testing methods for fetuses carrying copy number variants (CNVs) of 7q11.23 region.@*METHODS@#Prenatal cases with 7q11.23 microdeletion/microduplication detected by single nucleotide polymorphism array (SNP array) from January 2016 to June 2020 were retrospectively analyzed, including fetal ultrasound, chromosomal karyotype, SNP array, pregnancy outcome and follow-up. Literature on 7q11.23 CNVs identified upon prenatal diagnosis was also reviewed.@*RESULTS@#Five fetuses were found with 7q11.23 CNVs, including 3 microdeletions and 2 microduplications. Of them, 4 had ultrasonographic anomalies. The karyotypes of all fetuses were normal. Of three 7q11.23 microdeletions, two were de novo, while the remaining one couple did not accept parental verification. Of two 7q11.23 microduplications, one was de novo and the another was inherited from a phenotypic normal father. Three 7q11.23 microdeletions and one de novo 7q11.23 microduplication were electively aborted. One fetus carrying paternally inherited 7q11.23 microduplication was delivered full term. Follow-up found the infant had a normal phenotype.@*CONCLUSION@#Fetuses with 7q11.23 microdeletions or microduplications showed phenotypic heterogeneity. SNP array can accurately detect 7q11.23 CNVs, thereby provide accurate information for prenatal diagnosis and genetic counseling.


Subject(s)
DNA Copy Number Variations , Female , Fetus , Humans , Karyotyping , Pregnancy , Prenatal Diagnosis , Retrospective Studies
17.
Article in Chinese | WPRIM | ID: wpr-921996

ABSTRACT

OBJECTIVE@#To analyze the prenatal ultrasound phenotypes of copy number variations (CNVs) in different regions of 22q11.2, their parental original, and pregnancy outcome.@*METHODS@#Prenatal phenotypes of 25 cases with CNVs of the 22q11.2 region detected by chromosomal microarray analysis (CMA) was reviewed, which including There were 13 deletions and 12 duplications. Multiplex ligation-dependent probe amplification(MLPA) was carried out to determine their parental origin. All cases were followed up for their pregnancy outcome and postnatal growth.@*RESULTS@#Among the 25 cases, the ultrasound phenotypes of those involving the TBX1 gene were mostly cardiovascular system abnormalities, the ultrasound phenotypes of cases involving CRKL gene are mostly polycystic renal dysplasia. The ultrasound phenotypes of CNVs in the distal region (involving the SMARCB1 gene) are nervous system abnormalities. 12 cases (48%) of CNVs were de novo in origin. Five cases were lost during follow-up,12 had opted to terminate the pregnancy, 8 fetuses were born,7 with normal growth and development, 1 case with CNV in A-D region was abnormal.Prenatal ultrasound showed abnormalities in the cardiovascular system consistent with postnatal ultrasound, in addition with dysphagia and growth retardation.@*CONCLUSION@#Prenatal phenotypes of the 22q11.2 region CNVs are diverse, which may be related to gene function. NT thickening may be used as an early ultrasound finding of proximal 22q11.2 CNV. More research is still required to delineate the nature of CNVs and gene function, so as to facilitate genetic counseling.


Subject(s)
DNA Copy Number Variations , Female , Fetus , Genetic Counseling , Humans , Microarray Analysis , Phenotype , Pregnancy , Prenatal Diagnosis
18.
Article in Chinese | WPRIM | ID: wpr-921994

ABSTRACT

OBJECTIVE@#To assess the clinical value of non-invasive prenatal testing (NIPT) for the screening of trisomy and copy number variations (CNVs) of chromosomes 21, 18 and 13.@*METHODS@#From January 2015 to December 2019, 40 628 pregnant women underwent NIPT testing using high-throughput sequencing and bioinformatics analysis to test the cell-free fetal DNA in maternal plasma. High-risk pregnant women underwent invasive prenatal diagnosis, while low-risk ones were followed up by telephone.@*RESULTS@#The three most common indications included intermediate risk of serological screening, high risk of serological screening and advanced maternal age. Among all pregnant women, 257 cases were detected as trisomy 21, 18 and 13 (170, 49 and 38 cases, respectively). 227 cases chose invasive prenatal diagnosis, with respectively 122, 28 and 10 cases confirmed. The positive predictive value (PPV) was 81.33% (122/150), 65.12% (28/43), 29.41% (10/34), respectively. Two false negative cases of trisomy 18 were found during follow-up. Meanwhile, NIPT has detected 46 cases (15, 16 and 15 cases, respectively) CNVs on chromosomes 21, 18 and 13, among which 37 cases underwent invasive prenatal diagnosis. There were 5, 3 and 5 positive cases, which yielded a PPV of 41.67% (5/12), 25%(3/12) and 33.33%(5/15), respectively. Two other chromosome CNVs were accidentally discovered among the false positive samples.@*CONCLUSION@#The incidence of chromosomal abnormalities in the serological screening high-risk group was 52.02%, which was significantly higher than other groups. NIPT has a high sensitivity and specificity for the screening of trisomies 21, 18 and 13, while its accuracy for detecting CNVs of chromosomes 21, 18 and 13 needs to be improved. As a screening method, NIPT has a great clinical value, though there are still limitations of false positive and false negative results.Comprehensive pre- and post-test genetic counseling should be provided to the patients.


Subject(s)
Aneuploidy , Chromosome Disorders/genetics , Chromosomes , DNA Copy Number Variations , Down Syndrome/genetics , Female , Humans , Pregnancy , Prenatal Diagnosis , Trisomy/genetics , Trisomy 18 Syndrome/genetics
19.
Article in Chinese | WPRIM | ID: wpr-921981

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a girl with febrile convulsion as the main manifestation.@*METHODS@#The child was subjected to whole exome sequencing (WES) and copy number variation sequencing(CNV-seq). Fluorescence quantitative PCR was carried out to validate the microdeletion in her family.@*RESULTS@#The 7-year-old girl was diagnosed with febrile convulsion (complex type) for having fever for 3 days, mild cough and low thermal convulsion once. Her father, mother and aunt also had a history of febrile convulsion. A heterozygous deletion with a size of approximately 1.5 Mb was detected in the 16p13.11 region by WES and CNV-seq. The deletion has derived from her father and was confirmed by fluorescence quantitative PCR.@*CONCLUSION@#16p13.11 microdeletion syndrome has significant clinical heterogeneity. Different from those with epilepsy, mental retardation, autism, multiple malformations, carriers of 16p13.11 deletion may only manifest with febrile convulsion. Deletion of certain gene(s) from the region may be related to febrile convulsion and underlay the symptom of this child.


Subject(s)
Child , DNA Copy Number Variations , Epilepsy , Female , Humans , Seizures/genetics , Seizures, Febrile/genetics , Whole Exome Sequencing
20.
Article in Chinese | WPRIM | ID: wpr-921971

ABSTRACT

OBJECTIVE@#To explore the genetic basis of three families with recurrence of non-immune hydrops fetalis (NIHF) but negative result by copy number variation sequencing (CNV-seq).@*METHODS@#Amniotic fluid sample and/or abortive tissues of the fetuses were collected and subjected to CNV-seq analysis. Peripheral blood samples of the parents were also taken for trio whole exome sequencing (trio WES).@*RESULTS@#Fetus 1 was found to harbor heterozygous c.976G>T(p.Glu326*) variant of the SOX18 gene in addition with compound heterozygous variants c.844C>T(p.Arg282Trp) and c.9472+1G>A of the RYR1 gene. The three variants were all inherited from its parents and have been associated with the etiology of NIHF. Based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines, the c.976G>T variant of SOX18 gene and c.9472+1G>A of RYR1 gene were predicted to be pathogenic (PVS1+PM2+PP3+PP4, PVS1+PM2+PP3), and c.844C>T variant of RYR1 gene to be likely pathogenic (PM1+PM2+PP3). Fetus 2 was found to harbor compound heterozygous variants c.6682C>T(p.Gln2228*) and c.4373_4383del(p.Val1458Alafs*63) of the PIEZO1 gene. Both variants were also inherited from its parents and are associated with the etiology of NIHF. Based on ACMG standards and guidelines, both c.6682C>T and c.4373_4383del variants of PIEZO1 gene were predicted to be pathogenic (PVS1+PM2+PP4, PVS1+PM2). Fetus 3 was found to harbor compound heterozygous variants of the TTN gene c.29860G>C(p.Asp9954His) and c.21107A>T(p.Asp7036Val), which were respectively inherited from its parents. Both variants have been strongly associated with the phenotype, though the connection between the etiology of NIHF and variants of the TTN gene remains elusive. Based on ACMG standards and guidelines, the c.29860G>C and c.21107A>T variants of TTN gene were predicted to be likely pathogenic (PM1+PM2+PP3).@*CONCLUSION@#Trio WES can improve the diagnosis rate of NIHF with a negative result by CNV-seq. Considering the urgency of prenatal diagnosis, CNV-seq and trio WES should be carried out at the same time for fetuses with NIHF.


Subject(s)
DNA Copy Number Variations , Female , Genomics , Heterozygote , Humans , Hydrops Fetalis/genetics , Ion Channels , Pregnancy , SOXF Transcription Factors , United States , Whole Exome Sequencing
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