scholarly journals Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate

2016 ◽  
Vol 9 (1) ◽  
Author(s):  
Wu-Lin Charng ◽  
Ender Karaca ◽  
Zeynep Coban Akdemir ◽  
Tomasz Gambin ◽  
Mehmed M. Atik ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Molecular Diagnosis ◽  
High Potential ◽  
Neurologic Disease ◽  
Diagnosis Rate

scholarly journals Accurate Molecular Diagnosis of Gaucher Disease Using Clinical Exome Sequencing as a First-Tier Test

2021 ◽  
Vol 22 (11) ◽  
pp. 5538
Author(s):  
Stefania Zampieri ◽  
Silvia Cattarossi ◽  
Eleonora Pavan ◽  
Antonio Barbato ◽  
Agata Fiumara ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Molecular Diagnosis ◽  
Gaucher Disease ◽  
Novel Mutation ◽  
Large Deletion ◽  
Clinical Exome Sequencing ◽  
Number Variation ◽  
Long Range Pcr ◽  
Set Up ◽  
Beta Glucosidase

Gaucher disease (GD) is an autosomal recessive lysosomal disorder due to beta-glucosidase gene (GBA) mutations. The molecular diagnosis of GD is complicated by the presence of recombinant alleles originating from a highly homologous pseudogene. Clinical exome sequencing (CES) is a rapid genetic approach for identifying disease-causing mutations. However, copy number variation and recombination events are poorly detected, and further investigations are required to avoid mis-genotyping. The aim of this work was to set-up an integrated strategy for GD patients genotyping using CES as a first-line test. Eight patients diagnosed with GD were analyzed by CES. Five patients were fully genotyped, while three were revealed to be homozygous for mutations that were not confirmed in the parents. Therefore, MLPA (multiplex ligation-dependent probe amplification) and specific long-range PCR were performed, and two recombinant alleles, one of them novel, and one large deletion were identified. Furthermore, an MLPA assay performed in one family resulted in the identification of an additional novel mutation (p.M124V) in a relative, in trans with the known p.N409S mutation. In conclusion, even though CES has become extensively used in clinical practice, our study emphasizes the importance of a comprehensive molecular strategy to provide proper GBA genotyping and genetic counseling.

scholarly journals Not Only Diagnostic Yield: Whole-Exome Sequencing in Infantile Cardiomyopathies Impacts on Clinical and Family Management

2021 ◽  
Vol 9 (1) ◽  
pp. 2
Author(s):  
Laura Pezzoli ◽  
Lidia Pezzani ◽  
Ezio Bonanomi ◽  
Chiara Marrone ◽  
Agnese Scatigno ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Molecular Diagnosis ◽  
Clinical Management ◽  
Genetic Diagnosis ◽  
Family Management ◽  
Whole Exome ◽  
Time To Diagnosis ◽  
The Mean ◽  
Mean Time

Whole-exome sequencing (WES) is a powerful and comprehensive tool for the genetic diagnosis of rare diseases, but few reports describe its timely application and clinical impact on infantile cardiomyopathies (CM). We conducted a retrospective analysis of patients with infantile CMs who had trio (proband and parents)-WES to determine whether results contributed to clinical management in urgent and non-urgent settings. Twenty-nine out of 42 enrolled patients (69.0%) received a definitive molecular diagnosis. The mean time-to-diagnosis was 9.7 days in urgent settings, and 17 out of 24 patients (70.8%) obtained an etiological classification. In non-urgent settings, the mean time-to-diagnosis was 225 days, and 12 out of 18 patients (66.7%) had a molecular diagnosis. In 37 out of 42 patients (88.1%), the genetic findings contributed to clinical management, including heart transplantation, palliative care, or medical treatment, independent of the patient’s critical condition. All 29 patients and families with a definitive diagnosis received specific counseling about recurrence risk, and in seven (24.1%) cases, the result facilitated diagnosis in parents or siblings. In conclusion, genetic diagnosis significantly contributes to patients’ clinical and family management, and trio-WES should be performed promptly to be an essential part of care in infantile cardiomyopathy, maximizing its clinical utility.

Targeted exome sequencing and chromosomal microarray for the molecular diagnosis of nevoid basal cell carcinoma syndrome

2017 ◽  
Vol 86 (3) ◽  
pp. 206-211 ◽  
Author(s):  
Yoshihiro Matsudate ◽  
Takuya Naruto ◽  
Yumiko Hayashi ◽  
Mitsuyoshi Minami ◽  
Mikiko Tohyama ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Exome Sequencing ◽  
Molecular Diagnosis ◽  
Basal Cell ◽  
Chromosomal Microarray ◽  
Targeted Exome Sequencing

scholarly journals Clinical exome sequencing in neurologic disease

2016 ◽  
Vol 6 (2) ◽  
pp. 164-176 ◽  
Author(s):  
Brent L. Fogel ◽  
Saty Satya-Murti ◽  
Bruce H. Cohen
Keyword(s):  
Exome Sequencing ◽  
Neurologic Disease ◽  
Clinical Exome Sequencing

scholarly journals Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy

2016 ◽  
Vol 18 (9) ◽  
pp. 898-905 ◽  
Author(s):  
Katherine L. Helbig ◽  
Kelly D. Farwell Hagman ◽  
Deepali N. Shinde ◽  
Cameron Mroske ◽  
Zöe Powis ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Molecular Diagnosis ◽  
Significant Proportion ◽  
Patients With Epilepsy

scholarly journals Value of Exome Sequencing in Diagnosis and Management of Recurrent Non-immune Hydrops Fetalis: A Retrospective Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinyao Zhou ◽  
Jia Zhou ◽  
Xing Wei ◽  
Ruen Yao ◽  
Yingjun Yang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Pregnancy Outcome ◽  
Molecular Diagnosis ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Hydrops Fetalis ◽  
Intrauterine Fetal Death ◽  
Fetal Therapy ◽  
Inborn Errors ◽  
Prenatal Management

The purpose of the study was to use exome sequencing (ES) to study the contribution of single-gene disorders to recurrent non-immune hydrops fetalis (NIHF) and retrospectively evaluate the value of genetic diagnosis on prenatal management and pregnancy outcome. From January 2012 to October 2018, a cohort of 28 fetuses with recurrent NIHF was analyzed by trio ES. Fetuses with immune hydrops, non-genetic factors (including infection, etc.), karyotype, or CNV abnormalities were excluded. Variants were interpreted based on ACMG/AMP guidelines. Fetal therapy was performed on seven fetuses. Of the 28 fetuses, 10 (36%) were found to carry causal genetic variants (pathogenic or likely pathogenic) in eight genes (GBA, GUSB, GBE1, RAPSN, FOXC2, PIEZO1, LZTR1, and FOXP3). Five (18%) fetuses had variant(s) of uncertain significance (VUS). Of the 10 fetuses with definitive molecular diagnosis, five (50%) were diagnosed with inborn errors of metabolism. Among the seven fetuses who received fetal therapy, two had definitive molecular diagnosis and resulted in neonatal death. Among the remaining five fetuses with negative results, four had newborn survival and one had intrauterine fetal death. Trio ES could facilitate genetic diagnosis of recurrent NIHF and improve the prenatal management and pregnancy outcome.

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