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 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 Case Report: Candidate Genes Associated With Prenatal Ultrasound Anomalies in a Fetus With Prenatally Detected 1q23.3q31.2 Deletion

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiahao Song ◽  
Qian Zhang ◽  
Bing Lu ◽  
Zhongshan Gou ◽  
Ting Wang ◽  
...  
Keyword(s):  
Case Report ◽  
Prenatal Diagnosis ◽  
Fetal Growth ◽  
Coronary Sinus ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Phenotype Correlation ◽  
Renal Hypoplasia

Background: Patients with deletions involving the long arm of chromosome 1 are rare, and the main aim of this study was to refine the genotype-phenotype correlation.Case Report: In this report, a 28-year-old pregnant woman, gravida 2 para 1, at 25+4 weeks of gestation underwent ultrasound examination in our institute. The ultrasonographic findings of the fetus were as follows: (1) fetal growth restriction; (2) cleft lip and palate; (3) bilateral renal hypoplasia; (4) lateral ventriculomegaly; (5) single umbilical artery; (6) absent stomach; (7) coronary sinus dilatation with persistent left superior vena cava, ventricular septal defect and unroofed coronary sinus syndrome. Chromosomal microarray analysis of amniotic fluid from the fetus revealed a 28.025 Mb deletion in 1q23.3q31.2, spanning from position 164,559,675 to 192,584,768 (hg19).Conclusion: Genotype-phenotype correlation might improve prenatal diagnosis of fetuses with chromosome 1q deletion. PBX1 could be a candidate gene for fetal growth restriction, renal hypoplasia and congenital heart disease. Fetal growth restriction was accompanied by decreased renal volume in the fetus. Combined with ultrasonic examination, the application of chromosomal microarray analysis will provide accurate prenatal diagnosis.

scholarly journals Clinical application of chromosomal microarray analysis for fetuses with craniofacial malformations

2020 ◽  
Author(s):  
Chenyang Xu ◽  
Yanbao Xiang ◽  
Xueqin Xu ◽  
Lili Zhou ◽  
Huanzheng Li ◽  
...  
Keyword(s):  
Microarray Analysis ◽  
Genetic Basis ◽  
Chromosomal Abnormalities ◽  
Chromosome Analysis ◽  
Copy Number Variations ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Phenotype Correlation ◽  
Craniofacial Malformations ◽  
Clinically Significant

Abstract Background: The potential correlations between chromosomal abnormalities and craniofacial malformations (CFMs) remain a challenge in prenatal diagnosis. This study aimed to evaluate 118 fetuses with CFMs by applying chromosomal microarray analysis (CMA) and G-banded chromosome analysis. Results: Of the 118 cases in this study, 39.8% were isolated CFMs (47/118) whereas 60.2% were non-isolated CFMs (71/118). The detection rate of chromosomal abnormalities in non-isolated CFM fetuses was significantly higher than that in isolated CFM fetuses (26/71 vs. 7/47, p = 0.01). Compared to the 16 fetuses (16/104; 15.4%) with pathogenic chromosomal abnormalities detected by karyotype analysis, CMA identified a total of 33 fetuses (33/118; 28.0%) with clinically significant findings. These 33 fetuses included cases with aneuploidy abnormalities (14/118; 11.9%), microdeletion/microduplication syndromes (9/118; 7.6%), and other pathogenic copy number variations (CNVs) only (10/118; 8.5%).We further explored the CNV/phenotype correlation and found a series of clear or suspected dosage-sensitive CFM genes including TBX1, MAPK1, PCYT1A, DLG1, LHX1, SHH, SF3B4, FOXC1, ZIC2, CREBBP, SNRPB, and CSNK2A1.Conclusion: These findings enrich our understanding of the potential causative CNVs and genes in CFMs. Identification of the genetic basis of CFMs contributes to our understanding of their pathogenesis and allows detailed genetic counselling.

scholarly journals A Peruvian Child with 18p-/18q+ Syndrome and Persistent Microscopic Hematuria

2017 ◽  
Vol 06 (04) ◽  
pp. 258-266 ◽  
Author(s):  
Julio Poterico ◽  
Flor Vásquez ◽  
Miguel Chávez-Pastor ◽  
Milana Trubnykova ◽  
Félix Chavesta ◽  
...  
Keyword(s):  
Pericentric Inversion ◽  
Microscopic Hematuria ◽  
Clinical Variable ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Chromosome 18 ◽  
Phenotype Correlation ◽  
Recombinant Chromosome ◽  
Descending Aorta ◽  
Genomic Imbalances

AbstractChromosome 18 pericentric inversion carriers could have offspring with recombinant chromosomes, leading to patients with clinical variable manifestations. Patients with 18p-/18q+ rearrangements share some clinical characteristics, while other characteristics differ. Factors for such divergence include the length of the inverted segment, among others. Here, we describe a Peruvian child with dysmorphic features, intellectual disability persistent microscopic hematuria, aortic pseudocoarctation, and descending aorta arteritis, among others. Karyotype analysis of family members determined the mother as the carrier of a pericentric inversion: 18[inv(18)(p11.2q21.3)]. This child carries a recombinant chromosome 18, with chromosomal microarray analysis detecting two genomic imbalances in patient's chromosome 18: one duplicated region and one deleted segment in the large and the short arms, respectively. Persistent microscopic hematuria has not been reported among 18p-/18q+ phenotypes. Our patient elucidates that other factors play significant and yet unknown roles for not fulfilling the proposed genotype–phenotype correlation associated with hemizygosity in this type of recombinant chromosome 18 or presenting these features as the patient ages.

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.

scholarly journals A prenatal diagnosis case of partial duplication 21q21.1-q21.2 with normal phenotype maternally inherited

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Chunyan Jin ◽  
Zhiping Gu ◽  
Xiaohan Jiang ◽  
Pei Yu ◽  
Tianhui Xu
Keyword(s):  
Down Syndrome ◽  
Pregnant Woman ◽  
Prenatal Testing ◽  
Chromosome 21 ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Serological Screening ◽  
Partial Duplication ◽  
Her Family ◽  
Clinical Consequences

Abstract Background Down syndrome is characterized by trisomy 21 or partial duplication of chromosome 21. Extensive studies have focused on the identification of the Down Syndrome Critical Region (DSCR). We aim to provide evidence that duplication of 21q21.1-q21.2 should not be included in the DSCR and it has no clinical consequences on the phenotype. Case presentation Because serological screening was not performed at the appropriate gestational age, noninvasive prenatal testing (NIPT) analysis was performed for a pregnant woman with normal prenatal examinations at 22 weeks of gestation. The NIPT results revealed a 5.8 Mb maternally inherited duplication of 21q21.1-q21.2. To assess whether the fetus also carried this duplication, ultrasound-guided amniocentesis was conducted, and the result of chromosomal microarray analysis (CMA) with amniotic fluid showed a 6.7 Mb duplication of 21q21.1-q21.2 (ranging from position 18,981,715 to 25,707,009). This partial duplication of 21q21.1-q21.2 in the fetus was maternally inherited. After genetic counseling, the pregnant woman and her family decided to continue the pregnancy. Conclusion Our case clearly indicates that 21q21.1-q21.2 duplication is not included in the DSCR and most likely has no clinical consequences on phenotype.

scholarly journals Clinical characterization of chromosome 5q21.1–21.3 microduplication: A case report

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 1123-1127
Author(s):  
Shuang Chen ◽  
Yang Yu ◽  
Han Zhang ◽  
Leilei Li ◽  
Yuting Jiang ◽  
...  
Keyword(s):  
Case Report ◽  
Microarray Analysis ◽  
Prenatal Testing ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Chromosome 5 ◽  
Left Lateral Ventricle ◽  
Pulsed Doppler Ultrasound

AbstractChromosomal microdeletions and microduplications likely represent the main genetic etiologies for children with developmental delay or intellectual disability. Through prenatal chromosomal microarray analysis, some microdeletions or microduplications can be detected before birth to avoid unnecessary abortions or birth defects. Although some microdeletions or microduplications of chromosome 5 have been reported, numerous microduplications remain undescribed. We describe herein a case of a 30-year-old woman carrying a fetus with a chromosome 5q21.1–q21.3 microduplication. Because noninvasive prenatal testing indicated a fetal chromosome 5 abnormality, the patient underwent amniocentesis at 22 weeks 4 days of gestation. Karyotyping and chromosomal microarray analysis were performed on amniotic fluid cells. Fetal behavioral and structural abnormalities were assessed by color and pulsed Doppler ultrasound. Clinical characteristics of the newborn were assessed during the follow-up. The left lateral ventricle appeared widened on ultrasound, but the infant appeared normal at birth. The 5q21.1–q21.3 microduplication in the fetus was inherited from his mother. There are seven genes in this duplication region, but their main functions are unclear. According to this case report, microduplication in this region could represent a benign mutation. Clinicians should pay attention to the breakpoints and the genes involved when counseling patients with microdeletions and microduplications.

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