Expanding the genotype-phenotype correlation in subtelomeric 19p13.3 microdeletions using high resolution clinical chromosomal microarray analysis

2013 ◽  
Vol 161 (12) ◽  
pp. 2953-2963 ◽  
Author(s):  
Sirisha Peddibhotla ◽  
Mohamed Khalifa ◽  
Frank J. Probst ◽  
Jennifer Stein ◽  
Leslie L. Harris ◽  
...  
Keyword(s):  
High Resolution ◽  
Microarray Analysis ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation

scholarly journals 15q23 Gain in a Neonate with a Giant Omphalocele and Multiple Co-Occurring Anomalies

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Hui-Fang Zhou ◽  
Christopher J. O’Conor ◽  
Chiraag Gangahar ◽  
Louis P. Dehner
Keyword(s):  
High Resolution ◽  
Abdominal Wall ◽  
Microarray Analysis ◽  
Abdominal Wall Defect ◽  
Conventional Technique ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Genetic Abnormality ◽  
Initial Report ◽  
Giant Omphalocele

Background. Omphalocele is a rare congenital abdominal wall defect. It is frequently associated with genetic abnormality and other congenital anomalies, although isolated omphalocele cases do exist. Data have shown that omphalocele with co-occurring genetic abnormality has worse prognosis than isolated omphalocele. Chromosomal analysis by a conventional technique such as karyotyping can only detect aneuploidy and large segmental duplication or deletion. Newer techniques such as high-resolution microarray analysis allow for the study of alterations in chromosomal segments that are less than 5 Mb in length; this has led to identification of critical region and genes in the pathogenesis of omphalocele. Case Presentation. The current study is the initial report of a newborn male with a 15q23 gain and a giant omphalocele. High-resolution chromosomal microarray analysis identified this gain of copy number spanned 676 kb, involving almost the entire NOX5 gene (except for exon 1 of the longer transcript), the entirety of the EWSAT1, GLCE, PAQR5, KIF23, RPLP1, and DRAIC genes and exons 1–3 of the PCAT29 gene. Conclusion. To date, this is the first report of an associated 15q23 gain in a case with omphalocele. Interestingly, Giancarlo Ghiselli and Steven A Farber have reported that GLCE knockdown impairs abdominal wall closure in zebrafish. We also identified GLCE gene alteration in our case. This highlights the importance of GLCE in abdominal wall development. Further study of the function of GLCE and other genes might lead to a better understanding of the molecular mechanism of omphalocele.

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 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.

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