Carrier state for the nebulin exon 55 deletion and abnormal prenatal ultrasound findings as potential signs of nemaline myopathy

2012 ◽  
Vol 32 (1) ◽  
pp. 70-74 ◽  
Author(s):  
Hagith Yonath ◽  
Haike Reznik-Wolf ◽  
Michal Berkenstadt ◽  
Shlomit Eisenberg-Barzilai ◽  
Vilma-Lotta Lehtokari ◽  
...  
Keyword(s):  
Nemaline Myopathy ◽  
Carrier State ◽  
Prenatal Ultrasound ◽  
Ultrasound Findings

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 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.

Abnormal prenatal ultrasound findings in mevalonic aciduria

2008 ◽  
Vol 28 (3) ◽  
pp. 257-258 ◽  
Author(s):  
V. Schwarzer ◽  
D. Haas ◽  
G. F. Hoffmann ◽  
H. Meyberg ◽  
U. Gembruch
Keyword(s):  
Prenatal Ultrasound ◽  
Ultrasound Findings ◽  
Mevalonic Aciduria

Prenatal ultrasound findings observed in the Wolf-hirschhorn syndrome: Data from the registry of congenital malformations in auvergne

2013 ◽  
Vol 97 (12) ◽  
pp. 806-811 ◽  
Author(s):  
Anne Debost-Legrand ◽  
Carole Goumy ◽  
Hélène Laurichesse-Delmas ◽  
Pierre Déchelotte ◽  
Anne-Marie Beaufrère ◽  
...  
Keyword(s):  
Congenital Malformations ◽  
Prenatal Ultrasound ◽  
Ultrasound Findings

scholarly journals Restrictive dermopathy and associated prenatal ultrasound findings: case report

1997 ◽  
Vol 10 (2) ◽  
pp. 140-141 ◽  
Author(s):  
J. G. van der Stege ◽  
H. L. M. van Straaten ◽  
A. C. van der Walt ◽  
J. van Eyck
Keyword(s):  
Case Report ◽  
Prenatal Ultrasound ◽  
Ultrasound Findings ◽  
Restrictive Dermopathy

Novel Risk Score for Fetuses with Congenital Diaphragmatic Hernia Based on Ultrasound Findings

2019 ◽  
Vol 30 (01) ◽  
pp. 051-058
Author(s):  
Keita Terui ◽  
Kouji Nagata ◽  
Masahiro Hayakawa ◽  
Hiroomi Okuyama ◽  
Shoichirou Amari ◽  
...  
Keyword(s):  
Prediction Model ◽  
Congenital Diaphragmatic Hernia ◽  
Risk Score ◽  
Diaphragmatic Hernia ◽  
Validation Cohort ◽  
Prenatal Ultrasound ◽  
Odds Ratios ◽  
Ultrasound Findings ◽  
Liver Herniation ◽  
Thoracic Stomach

Abstract Introduction We aimed to establish and validate a risk score for fetuses with congenital diaphragmatic hernia (CDH) using only prenatal ultrasound findings. Material and Methods Derivation (2011–2016, n = 350) and validation (2006–2010, n = 270) cohorts were obtained from a Japanese CDH study group database. Using a logistic regression analysis, we created a prediction model and weighted scoring system from the derivation dataset and calculated the odds ratio of an unsatisfactory prognosis (death within 90 days of life or hospitalization duration exceeding 180 days). Five adverse prognostic factors obtained using prenatal ultrasound, including an observed/expected lung area-to-head circumference ratio (o/eLHR) <25%, liver herniation occupying more than one-third of the thoracic space, thoracic stomach, right-side CDH, and severe malformations, were used as predictors. The obtained model was validated using the validation cohort. Results The unsatisfactory prognosis prediction model was obtained based on the adjusted odds ratios. The C statistics of the model were 0.83 and 0.80 in the derivation and validation datasets, respectively. The five variables were weighted proportionally to their adjusted odds ratios for an unsatisfactory prognosis (o/eLHR <25%, 1 point; liver herniation occupying more than one-third of the thoracic space, 1 point; thoracic stomach, 1 point; right-side CDH, 2 points; and severe malformations, 3 points). Unsatisfactory prognosis rates for the low- (0–2 points), intermediate- (3–5 points), and high-risk (6–8 points) groups were 17, 46, and 100%, respectively (p < 0.001), in the validation cohort. Conclusion Our simple risk score effectively predicted the prognosis of fetuses with CDH.

Congenital Bowing of Long Bones: Prenatal Ultrasound Findings and Diagnostic Dilemmas

2002 ◽  
Vol 17 (4) ◽  
pp. 236-239 ◽  
Author(s):  
Chantal Farra ◽  
Caroline Piquet ◽  
Marc Guillaume ◽  
Claude D’Ercole ◽  
Nicole Philip
Keyword(s):  
Prenatal Ultrasound ◽  
Long Bones ◽  
Ultrasound Findings

PRENATAL ULTRASOUND FINDINGS IN HYDROLETHALUS: CONTINUING DIFFICULTIES IN DIAGNOSIS

1996 ◽  
Vol 16 (2) ◽  
pp. 173-179 ◽  
Author(s):  
MICHAEL NORGARD ◽  
JEROME YANKOWITZ ◽  
WILLIAM RHEAD ◽  
ADAM B. KANIS ◽  
BRYAN D. HALL
Keyword(s):  
Prenatal Ultrasound ◽  
Ultrasound Findings
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