ABSTRACT
Objective@#To assess the application value of chromosomal microarray analysis (CMA) for prenatal diagnosis of fetus with ultrasound abnormalities.@*Methods@#For 293 fetuses with ultrasound abnormalities (including 168 with structural abnormalities and 125 with non-structured abnormalities) but no common chromosomal abnormalities, CMA assay was performed.@*Results@#Sixteen pathogenic copy number variants (pCNVs) were detected by CMA with a detection rate of 5.46%. The detection rates were 5.95% (10/168) for those with structural abnormalities and 4.80% (6/125) for those with non-structural abnormalities.@*Conclusion@#Compared with conventional karyotyping analysis, CMA can improve the detection of fetal chromosomal abnormality and provide an effective means for prenatal diagnosis.
ABSTRACT
Objective@#To explore the application of chromosomal microarray analysis (CMA) in neonatal birth defects and further determine the frequency of chromosome imbalances in neonates with birth defects.@*Methods@#Retrospective analysis was performed in 121 neonates with specific features, such as distinctive facial features, congenital heart disease, congenital malformation, neonatal decreased responsive, hypotonia, seizures and others at the Department of Neonatology, Guangdong Women and Children Hospital from May 2016 to November 2017.All the cases were analyzed by using chromosomal microarray analysis (CMA).@*Results@#A total of 23 (19.0%) patients were identified with pathogenic CNVs, 3 patients (2.5%) with uncertain clinical significant CNVs.There were 5 patients (4.1%)with chromosome numerical abnormalities, 12 patients (9.9%)with microdeletion/microduplication syndrome, 6 patients (5.0%) with chromosome deletion or duplication.All groups whose incidence was sorted from high to low were facial characters(30.3%), congenital malformation(21.6%), neonatal decreased responsive(9.1%) and other indications(6.7%).@*Conclusions@#CMA is a valuable clinical diagnostic tool that allows precise identification of chromosome imbalances as the cause of birth defects in neonates.CMA can detect many more clinically relevant genomic abnormalities than conventional cytogenetic study and assist the clinician in diagnosis, early neonatal intervention, and genetic counseling.
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Objective@#To report on a case of maternally derived 45, X mosaicism detected by non-invasive prenatal testing (NIPT).@*Methods@#Fetal sex chromosomal abnormality was detected by NIPT. Maternally derived 45, X mosaicism was confirmed by chromosome karyotype analysis. Fetal sex chromosome aneuploidy was detected by amniotic fluid chromosome microarray analysis.@*Results@#A maternal 45, X mosaicism was diagnosed. The fetus was confirmed to be normal.@*Conclusion@#Maternal 45, X masaicism can be diagnosed by NIPT.
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Objective@#To investigate the genetic etiology of neurodevelopmental disorders (NDD), and to provide a theoretical basis for its genetic counseling, family risk evaluation and prenatal diagnosis.@*Methods@#Karyotype analysis and chromosome microarray analysis (CMA) were conducted of the data from 420 children diagnosed accor-ding to NDD diagnostic criteria at Maternal and Child Health Hospital of Hunan Province from January 2016 to December 2018.@*Results@#Among the 420 cases, 14 cases (3.33%, 14/420 cases) with global developmental disabilities/intellectual disabilities (GDD/ID) had chromosomal abnormalities.The location of chromosome breakpoints and the range of deleted or duplicated fragments in 13 cases were further determined by using CMA.In this study, pathogenic copy number variations (CNVs) were detected in 61 children (14.52%, 61/420 cases), which included 31 cases (50.82%, 31/61 cases) of known syndromes, including Angelman/Prader-Will syndrome (8 cases), Williams syndrome (3 cases), Phelan-McDermid syndrome (3 cases) and other 13 syndromes, and 30 cases with clinically significant pathogenic CNVs.Additionally, by the combination of CMA and fluorescence in situ hybridization (FISH), a family were diagnosed with mental retardation caused by 10q26 and 12p13 occult rearrangement.@*Conclusions@#Chromosomal abnormalities and genomic microdeletion/duplication are the primary genetic causes for children with NDD.Combination of karyotype analysis, CMA and FISH can provide definite etiological diagnosis for these children, which has important clinical signi-ficance for the treatment of children and guidance of their parents′ reproduction.
ABSTRACT
Chromosome microarray analysis (CMA) is a cost-effective molecular cytogenetic technique that has been used as a first-line diagnostic test in neurodevelopmental disorders in the USA since 2011. The impact of CMA results on clinical practice in China is not yet well studied, so we aimed to better evaluate this phenomenon. We analyzed the CMA results from 434 patients in our clinic, and characterized their molecular diagnoses, clinical features, and follow-up clinical actions based on these results. The overall diagnostic yield for our patients was 13.6% (59 out of 434). This gave a detection rate of 14.7% for developmental delay/intellectual disability (DD/ID, 38/259) and 12% for autism spectrum disorders (ASDs, 21/175). Thirty-three recurrent (n ≥ 2) variants were found, distributed at six chromosomal loci involving known chromosome syndromes (such as DiGeorge, Williams Beuren, and Angelman/Prader-Willi syndromes). The spectrum of positive copy number variants in our study was comparable to that reported in Caucasian populations, but with specific characteristics. Parental origin tests indicated an effect involving a significant maternal transmission bias to sons. The majority of patients with positive results (94.9%) had benefits, allowing earlier diagnosis (36/59), prioritized full clinical management (28/59), medication changes (7/59), a changed prognosis (30/59), and prenatal genetic counseling (15/59). Our results provide information on de novo mutations in Chinese children with DD/ID and/or ASDs. Our data showed that microarray testing provides immediate clinical utility for patients. It is expected that the personalized medical care of children with developmental disabilities will lead to improved outcomes in long-term developmental potential. We advocate using the diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility.