Dataset Information

Prenatal detection of terminal 9p24.3 microduplication encompassing DOCK8 gene: A variant of likely benign.

ABSTRACT:

Abstract

Trisomy 9p is one of the most common chromosomal partial trisomies in newborns. However, reports on prenatal 9p microduplications are rare in the clinic. This study aimed to examine the genotype-phenotype correlation and assess the clinical significance of 9p24.3 microduplication encompassing the DOCK8 gene. Eight pregnant women underwent amniocentesis for cytogenetic and genetic testing for various indications for prenatal diagnosis from January 2019 to January 2020. Chromosomal karyotypic analysis was performed on G-band metaphases that were prepared from cultured amniotic fluid cells. Chromosomal microarray analysis was carried out to detect chromosomal copy number variations. We also performed a literature review on clinical data on similar 9p24.3 microduplications to determine the genotype-phenotype correlation. We detected 123-248-kb microduplications in the region of 9p24.3 (chr9: 208454-469022), involving part of or the entire DOCK8 gene. The indications for prenatal diagnosis mainly focused on the risk of maternal serum screening for trisomy 21/18, advanced maternal age, and increased nuchal translucency. No evident structural abnormalities were observed for all fetuses, except for case 5 who presented with increased nuchal translucency in prenatal ultrasound findings. Follow-up of postnatal health was performed and showed no apparent abnormalities for cases 1 to 6 after birth. The parents of case 7 chose to terminate the pregnancy while the parents of case 8 chose to continue the pregnancy. We propose that 9p24.3 microduplications that encompass part of or the entire DOCK8 gene are variants that might be benign. However, further large-scale studies are necessary to evaluate the clinical pathogenicity. For prenatal cases with 9p24.3 microduplication, postnatal health and growth should be followed up and assessed regularly from childhood to adulthood.

SUBMITTER: Yue F

PROVIDER: S-EPMC7837864 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Prenatal detection of terminal 9p24.3 microduplication encompassing DOCK8 gene: A variant of likely benign.

Yue Fagui F Yu Yang Y Zhang Xinyue X Jiang Yuting Y Li Leilei L Liu Ruizhi R Zhang Hongguo H

Medicine 20210101 3

<h4>Abstract</h4>Trisomy 9p is one of the most common chromosomal partial trisomies in newborns. However, reports on prenatal 9p microduplications are rare in the clinic. This study aimed to examine the genotype-phenotype correlation and assess the clinical significance of 9p24.3 microduplication encompassing the DOCK8 gene. Eight pregnant women underwent amniocentesis for cytogenetic and genetic testing for various indications for prenatal diagnosis from January 2019 to January 2020. Chromosoma ...[more]

PMID: 33545980

Similar Datasets

Project description:AbstractTrisomy 6q is a recognizable syndrome which exhibits psychomotor/growth retardation, developmental/intellectual disabilities, feeding difficulties, facial dysmorphism, hearing loss, brain and heart malformations. The purpose of this study was to delineate the prenatal features of proximal 6q14.1 duplication in fetal period, which was rarely reported in clinic. Eight pregnant women who opted for amniocentesis due to the fetal ultrasound abnormalities, maternal serum screening or other indications for prenatal diagnosis between 2019 and 2020. Chromosomal microarray analysis and G-banding analysis were offered after informed consents were obtained. Cytogenetic prenatal investigation showed all fetuses presented normal karyotypes except case 4 exhibiting a balanced chromosomal translocation 46,XX,t (4;8)(p16;q24). The chromosomal microarray analysis detected 0.211-0.242 Mb duplications of 6q14.1 (chr6: 80109532-80351666, hg19) in all 8 cases, encompassing the morbid gene LCA5 in common. Seven pregnant women (P1-P7) continued their pregnancies and delivered healthy infants at term while the parents of case 8 opted for termination of pregnancy for severe abnormal ultrasound findings. Overall, all neonates were in a good healthy condition with no evident anomalies, ranging from 2 m to 16 m. It is proposed that 6q14.1 duplication involving LCA5 gene detected in our study might be variants of likely benign. However, further large-scale studies should be gathered to assess its pathogenicity. To our knowledge, our study is the first report focusing on prenatally detected proximal 6q14.1 duplication, accompanied by detailed clinic phenotypes. Diverse ultrasound findings were observed in these cases, ranging from normal to abnormal. More evidence should be gathered to interpret the prenatal genotype-phenotype correlation of 6q14.1 duplication. For these cases with 6q14.1 microduplication, long term follow up should be carried out in case abnormal clinical symptoms or developmental-behavioral disorders emerge.

Project description:Background: Chromosomal 16p11.2 deletions and duplications are genomic disorders which are characterized by neurobehavioral abnormalities, obesity, congenital abnormalities and so on. However, the prenatal phenotypes of 16p11.2 copy number variations (CNVs) are still not well described till now. This study aimed to provide an elaborate summary of intrauterine phenotypic features for such genomic disorders. Methods: Twenty prenatal amniotic fluid samples diagnosed with 16p11.2 microdeletions/microduplications were obtained from pregnant women who opted for invasive prenatal testing. Karyotypic analysis and chromosomal microarray analysis (CMA) were performed in parallel. The pregnancy outcomes and health conditions after birth for all cases were followed up. Meanwhile, we made a pooled analysis on the prenatal phenotypes for the published cases carrying 16p11.2 CNVs. Results: 20 fetuses (20/20884, 0.10%) with 16p11.2 CNVs were identified: five 16p11.2 BP2-BP3 deletion, ten 16p11.2 BP4-BP5 deletion and five 16p11.2 BP4-BP5 duplication. Abnormal ultrasound findings were recorded in ten participants with 16p11.2 deletions.Various degrees of intrauterine phenotypic features, ranging from normal to abnormal, were observed. No ultrasound abnormalities were observed for all 16p11.2 duplication cases during the pregnancy period. For 16p11.2 deletions, eleven cases terminated their pregnancies. For 16p11.2 duplications, four cases gave birth to healthy neonates except one was lost to follow up. Conclusions: Diverse prenatal phenotypes were presented in 16p11.2 CNVs, ranging from normal to abnormal. For 16p11.2 BP4-BP5 deletion, the most common structural and non-structural abnormalities were the abnormality of the vertebral column or rib and thickened nuchal translucency, respectively. 16p11.2 BP2-BP3 deletion might be closely associated with fetal growth restriction and single umbilical artery. No representative ultrasound findings for 16p11.2 duplication were observed till now. Considering the variable expressivity and incomplete penetrance of 16p11.2 CNVs, long term follow up after birth should be carried out for these cases. We identified 20 fetuses carrying the 16p11.2 microdeletions and microduplications using chromosomal microarray analysis. And diverse prenatal phenotypes and the critical genes involved in the deleted/duplicated regions were described in this study.

Project description:BackgroundSeveral studies have reported on the clinical phenotype of the 17q12 microduplication syndrome, a rare autosomal dominant genetic disorder, in children and adults, but few have reported on its prenatal diagnosis. This study analyzed the prenatal ultrasound phenotypes of the 17q12 microduplication syndrome to improve the understanding, diagnosis, and monitoring of this disease in fetuses.MethodsA retrospective analysis of 8,200 pregnant women who had received an invasive antenatal diagnosis at tertiary referral hospitals between January 2016 and August 2021 was performed. Amniotic fluid or cord blood was sampled from the pregnant women for karyotyping and chromosome microarray analysis (CMA).ResultsThe CMA revealed microduplication in the 17q12 region of the genome in five fetuses, involving fragments of about 1.5-1.9 Mb. Five fetuses with the 17q12 microduplication syndrome had different prenatal ultrasound phenotypes, including duodenal obstruction (two fetuses); mild ventriculomegaly, dysplasia of the septum pellucidum, agenesis of the corpus callosum (one fetus); and a strong echo in the left ventricle only (one fetus). The ultrasound phenotype of one fetus was normal. Among the five fetuses with the 17q12 microduplication syndrome, the parents of three refused CNV segregation analysis, while CNV segregation analysis was performed for the remaining two fetuses to confirm whether the disorder was inherited maternally or paternally, with normal phenotypes. After genetic counseling, the parents of those two fetuses chose to terminate the pregnancy, while the parents of the three unverified fetuses continued the pregnancy, with normal follow-up after birth.ConclusionAlthough prenatal ultrasound phenotypes in fetuses with the 17q12 microduplication syndrome are highly variable, our study has highlighted the distinct association between duodenal obstruction and the 17q12 microduplication syndrome. Understanding the relationship between the pathogenesis of the 17q12 microduplication in prenatal ultrasound phenotypes and its long-term prognosis will contribute to better genetic counseling concerning the 17q12 microduplication syndrome, which is still a challenge.

Dataset Information

Prenatal detection of terminal 9p24.3 microduplication encompassing DOCK8 gene: A variant of likely benign.

Abstract

Publications

Prenatal detection of terminal 9p24.3 microduplication encompassing DOCK8 gene: A variant of likely benign.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets