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Prenatal diagnosis of 17q12 microdeletion and microduplication syndrome in fetuses with congenital renal abnormalities.

ABSTRACT: Background:Copy number variations (CNVs) involving the 17q12 region are associated with a broad range of clinical phenotypes. Deletion of the 17q12 chromosome results in structural or functional abnormalities in the kidney and urethra, type 5 diabetes (MODY5), and neurodevelopmental or neuropsychiatric disorders. Microduplication of 17q12 is rare and is associated with an increased risk of epilepsy and mental retardation. We studied the prenatal diagnosis of 17q12 microduplication and microdeletion syndrome in fetuses with congenital renal abnormalities. Case presentation:We conducted a retrospective analysis of prenatal diagnoses in our hospital from January 2016 to April 2018. Abnormal renal ultrasound findings were present in 126 fetuses and the incidence of chromosomal abnormalities was 10.32%(13/126). Conventional karyotyping detected 7 of 126 fetuses as aneuploid (5.56%). In addition, chromosome microarray analysis (CMA) detected 6 fetuses(4.76%) with copy number variations (CNVs), of which 5 were shown to have 17q12 microdeletion syndrome and 1 had 17q12 microduplication syndrome. We followed up these pregnant women. The results of the testing had a significant impact on pregnancy outcome. The phenotypes of 17q12 microdeletions and microduplications vary widely, affecting patients in different ways, such as language delays, social deficiencies, and even abortion. Conclusions:The characteristics of 17q12 microdeletions and microduplications are so vague that the condition is often misdiagnosed or missed. This study demonstrated that karyotype analysis combined with CMA can significantly improve the diagnostic rate in prenatal diagnosis of CNVs, which can provide evidence for genetic counseling in such pregnancies.

SUBMITTER: Wan S

PROVIDER: S-EPMC6525371 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Prenatal diagnosis of 17q12 microdeletion and microduplication syndrome in fetuses with congenital renal abnormalities.

Wan Shanning S Zheng Yunyun Y Dang Yinghui Y Song Tingting T Chen Biliang B Zhang Jianfang J

Molecular cytogenetics 20190517

<h4>Background</h4>Copy number variations (CNVs) involving the 17q12 region are associated with a broad range of clinical phenotypes. Deletion of the 17q12 chromosome results in structural or functional abnormalities in the kidney and urethra, type 5 diabetes (MODY5), and neurodevelopmental or neuropsychiatric disorders. Microduplication of 17q12 is rare and is associated with an increased risk of epilepsy and mental retardation. We studied the prenatal diagnosis of 17q12 microduplication and mi ...[more]

PMID: 31131025

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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.

Project description:BackgroundCongenital gastrointestinal obstruction (CGIO) mainly refers to the stenosis or atresia of any part from the esophagus to the anus and is one of the most common surgical causes in the neonatal period. The concept of genetic factors as an etiology of CGIO has been accepted, but investigations about CGIO have mainly focused on aneuploidy, and the focus has been on duodenal obstruction. The objective of this study was to evaluate the risk of chromosome aberrations (including numeric and structural aberrations) in different types of CGIO. A second objective was to assess the risk of abnormal CNVs detected by copy number variation sequencing (CNV-seq) in fetuses with different types of CGIO.MethodsData from pregnancies referred for invasive testing and CNV-seq due to sonographic diagnosis of fetal CGIO from 2015 to 2020 were obtained retrospectively from the computerized database. The rates of chromosome aberrations and abnormal CNV-seq findings for isolated CGIOs and complicated CGIOs and different types of CGIOs were calculated.ResultsOf the 240 fetuses with CGIO that underwent karyotyping, the detection rate of karyotype abnormalities in complicated CGIO was significantly higher than that of the isolated group (33.8% vs. 10.8%, p < 0.01). Ninety-three cases with normal karyotypes further underwent CNV-seq, and CNV-seq revealed an incremental diagnostic value of 9.7% over conventional karyotyping. In addition, the incremental diagnostic yield of CNV-seq analysis in complicated CGIOs (20%) was higher than that in isolated CGIOs (4.8%), and the highest prevalence of pathogenic CNVs/likely pathogenic CNVs was found in the duodenal stenosis/atresia group (17.5%), followed by the anorectal malformation group (15.4%). The 13q deletion, 10q26 deletion, 4q24 deletion, and 2p24 might be additional genetic etiologies of duodenal stenosis/atresia.ConclusionsThe risk of pathogenic chromosomal abnormalities and CNVs increased in the complicated CGIO group compared to that in the isolated CGIO group, especially when fetuses presented duodenal obstruction (DO) and anorectal malformation. CNV-seq was recommended to detect submicroscopic chromosomal aberrations for DO and anorectal malformation when the karyotype was normal. The relationship between genotypes and phenotypes needs to be explored in the future to facilitate prenatal diagnosis of fetal CGIO and yield new clues into their etiologies.

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Prenatal diagnosis of 17q12 microdeletion and microduplication syndrome in fetuses with congenital renal abnormalities.

Publications

Prenatal diagnosis of 17q12 microdeletion and microduplication syndrome in fetuses with congenital renal abnormalities.

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