scholarly journals Prenatal diagnosis of X-linked myopathy associated with aVMA21gene mutation afforded through a novel targeted exome sequencing strategy applied in fetuses with abnormal ultrasound findings

2017 ◽  
Vol 5 (3) ◽  
pp. 308-311 ◽  
Author(s):  
Christopher Konialis ◽  
Efstratios Assimakopoulos ◽  
Birgitta Hagnefelt ◽  
Sophia Karapanou ◽  
Alexandros Sotiriadis ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Exome Sequencing ◽  
Targeted Exome Sequencing ◽  
Ultrasound Findings ◽  
Sequencing Strategy

scholarly journals First applications of a targeted exome sequencing approach in fetuses with ultrasound abnormalities reveals an important fraction of cases with associated gene defects

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1955 ◽  
Author(s):  
Constantinos Pangalos ◽  
Birgitta Hagnefelt ◽  
Konstantinos Lilakos ◽  
Christopher Konialis
Keyword(s):  
Exome Sequencing ◽  
Genetic Disorders ◽  
Nemaline Myopathy ◽  
Prenatal Ultrasound ◽  
Fetal Ultrasound ◽  
Ehlers Danlos Syndrome ◽  
Targeted Exome Sequencing ◽  
Ultrasound Findings ◽  
Fetal Malformations ◽  
Ellis Van Creveld Syndrome

Background.Fetal malformations and other structural abnormalities are relatively frequent findings in the course of routine prenatal ultrasonographic examination. Due to their considerable genetic and clinical heterogeneity, the underlying genetic cause is often elusive and the resulting inability to provide a precise diagnosis precludes proper reproductive and fetal risk assessment. We report the development and first applications of an expanded exome sequencing-based test, coupled to a bioinformatics-driven prioritization algorithm, targeting gene disorders presenting with abnormal prenatal ultrasound findings.Methods.We applied the testing strategy to14 euploid fetuses, from 11 on-going pregnancies and three products of abortion, all with various abnormalities or malformations detected through prenatal ultrasound examination. Whole exome sequencing (WES) was followed by variant prioritization, utilizing a custom analysis pipeline (Fetalisalgorithm), targeting 758 genes associated with genetic disorders which may present with abnormal fetal ultrasound findings.Results.A definitive or highly-likely diagnosis was made in 6 of 14 cases (43%), of which 3 were abortuses (Ellis-van Creveld syndrome, Ehlers-Danlos syndrome and Nemaline myopathy 2) and 3 involved on-going pregnancies (Citrullinemia, Noonan syndrome,PROKR2-related Kallmann syndrome). In the remaining eight on-going pregnancy cases (57%), aZIC1variant of unknown clinical significance was detected in one case, while in seven cases testing did not reveal any pathogenic variant(s). Pregnancies were followed-up to birth, resulting in one neonate harboring thePROKR2mutation, presenting with isolated minor structural cardiac abnormalities, and in seven apparently healthy neonates.Discussion.The expanded targeted exome sequencing-based approach described herein (Fetalis), provides strong evidence suggesting a definite and beneficial increase in our diagnostic capabilities in prenatal diagnosis of otherwise chromosomally balanced fetuses with troubling ultrasound abnormalities. Furthermore, the proposed targeted exome sequencing strategy, designed primarily as a diagnostic rather than a research discovery tool, overcomes many of the problems and limitations associated with clinical wide-scale WES testing in a prenatal setting.

scholarly journals First applications of a targeted exome sequencing approach in fetuses with ultrasound abnormalities reveals an important fraction of cases with associated gene defects

2016 ◽  
Author(s):  
Constantinos Pangalos ◽  
Birgitta Hagnefelt ◽  
Konstantinos Lilakos ◽  
Christopher Konialis
Keyword(s):  
Exome Sequencing ◽  
Genetic Disorders ◽  
Nemaline Myopathy ◽  
Prenatal Ultrasound ◽  
Fetal Ultrasound ◽  
Ehlers Danlos Syndrome ◽  
Targeted Exome Sequencing ◽  
Ultrasound Findings ◽  
Fetal Malformations ◽  
Ellis Van Creveld Syndrome

Background : Fetal malformations and other structural abnormalities are relatively frequent findings in the course of routine prenatal ultrasonographic examination. Due to their considerable genetic and clinical heterogeneity, the underlying genetic cause is often elusive and the resulting inability to provide a precise diagnosis precludes proper reproductive and fetal risk assessment. We report the development and first applications of an expanded exome sequencing-based test, coupled to a bioinformatics-driven prioritization algorithm, targeting gene disorders presenting with abnormal prenatal ultrasound findings. Methods : We applied the testing strategy to14 euploid fetuses, from 11 on-going pregnancies and 3 products of abortion, all with various abnormalities or malformations detected through prenatal ultrasound examination. Whole exome sequencing (WES) was followed by variant prioritization, utilizing a custom analysis pipeline (Fetalis algorithm), targeting 758 genes associated with genetic disorders which may present with abnormal fetal ultrasound findings. Results :A definitive or highly-likely diagnosis was made in 6 of 14 cases (43%), of which 3 were abortuses (Ellis-van Creveld syndrome, Ehlers-Danlos syndrome and Nemaline myopathy 2) and 3 involved on-going pregnancies (Citrullinemia, Noonan syndrome, PROKR2-related Kallmann syndrome). In the remaining 8 on-going pregnancy cases (57%), a ZIC1 variant of unknown clinical significance was detected in one case, while in 7 cases testing did not reveal any pathogenic variant(s). Pregnancies were followed-up to birth, resulting in one neonate harboring the PROKR2 mutation, presenting with isolated minor structural cardiac abnormalities, and in 7 apparently healthy neonates. Discussion : The expanded targeted exome sequencing-based approach described herein (Fetalis), provides strong evidence suggesting a definite and beneficial increase in our diagnostic capabilities in prenatal diagnosis of otherwise chromosomally balanced fetuses with troubling ultrasound abnormalities. Furthermore, the proposed targeted exome sequencing strategy, designed primarily as a diagnostic rather than a research discovery tool, overcomes many of the problems and limitations associated with clinical wide-scale WES testing in a prenatal setting.

scholarly journals Rapid Prenatal Diagnosis Using Targeted Exome Sequencing

2019 ◽  
Vol 74 (4) ◽  
pp. 202-204
Author(s):  
Natalie Chandler ◽  
Sunayna Best ◽  
Jane Hayward ◽  
Francesca Faravelli ◽  
Sahar Mansour ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Exome Sequencing ◽  
Targeted Exome Sequencing

scholarly journals First applications of a targeted exome sequencing approach in fetuses with ultrasound abnormalities reveals an important fraction of cases with associated gene defects

2016 ◽  
Author(s):  
Constantinos Pangalos ◽  
Birgitta Hagnefelt ◽  
Konstantinos Lilakos ◽  
Christopher Konialis
Keyword(s):  
Exome Sequencing ◽  
Genetic Disorders ◽  
Nemaline Myopathy ◽  
Prenatal Ultrasound ◽  
Fetal Ultrasound ◽  
Ehlers Danlos Syndrome ◽  
Targeted Exome Sequencing ◽  
Ultrasound Findings ◽  
Fetal Malformations ◽  
Ellis Van Creveld Syndrome

Background : Fetal malformations and other structural abnormalities are relatively frequent findings in the course of routine prenatal ultrasonographic examination. Due to their considerable genetic and clinical heterogeneity, the underlying genetic cause is often elusive and the resulting inability to provide a precise diagnosis precludes proper reproductive and fetal risk assessment. We report the development and first applications of an expanded exome sequencing-based test, coupled to a bioinformatics-driven prioritization algorithm, targeting gene disorders presenting with abnormal prenatal ultrasound findings. Methods : We applied the testing strategy to14 euploid fetuses, from 11 on-going pregnancies and 3 products of abortion, all with various abnormalities or malformations detected through prenatal ultrasound examination. Whole exome sequencing (WES) was followed by variant prioritization, utilizing a custom analysis pipeline (Fetalis algorithm), targeting 758 genes associated with genetic disorders which may present with abnormal fetal ultrasound findings. Results :A definitive or highly-likely diagnosis was made in 6 of 14 cases (43%), of which 3 were abortuses (Ellis-van Creveld syndrome, Ehlers-Danlos syndrome and Nemaline myopathy 2) and 3 involved on-going pregnancies (Citrullinemia, Noonan syndrome, PROKR2-related Kallmann syndrome). In the remaining 8 on-going pregnancy cases (57%), a ZIC1 variant of unknown clinical significance was detected in one case, while in 7 cases testing did not reveal any pathogenic variant(s). Pregnancies were followed-up to birth, resulting in one neonate harboring the PROKR2 mutation, presenting with isolated minor structural cardiac abnormalities, and in 7 apparently healthy neonates. Discussion : The expanded targeted exome sequencing-based approach described herein (Fetalis), provides strong evidence suggesting a definite and beneficial increase in our diagnostic capabilities in prenatal diagnosis of otherwise chromosomally balanced fetuses with troubling ultrasound abnormalities. Furthermore, the proposed targeted exome sequencing strategy, designed primarily as a diagnostic rather than a research discovery tool, overcomes many of the problems and limitations associated with clinical wide-scale WES testing in a prenatal setting.

scholarly journals Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management

2018 ◽  
Vol 20 (11) ◽  
pp. 1430-1437 ◽  
Author(s):  
Natalie Chandler ◽  
Sunayna Best ◽  
Jane Hayward ◽  
Francesca Faravelli ◽  
Sahar Mansour ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prenatal Diagnosis ◽  
Exome Sequencing ◽  
Prenatal Counseling ◽  
Targeted Exome Sequencing ◽  
Potential Impact

A novel mutation identified in PKHD1 by targeted exome sequencing: Guiding prenatal diagnosis for an ARPKD family

Gene ◽  
2014 ◽  
Vol 551 (1) ◽  
pp. 33-38 ◽  
Author(s):  
Yan Xu ◽  
Bing Xiao ◽  
Wen-Ting Jiang ◽  
Lei Wang ◽  
Hong-quan Gen ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Exome Sequencing ◽  
Novel Mutation ◽  
Targeted Exome Sequencing
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