scholarly journals Clinical whole exome sequencing from dried blood spot identifies novel genetic defect underlying asparagine synthetase deficiency

2017 ◽  
Vol 6 (1) ◽  
pp. 200-205 ◽  
Author(s):  
Avinash Abhyankar ◽  
Michelle Lamendola-Essel ◽  
Kelly Brennan ◽  
Jessica L. Giordano ◽  
Cecilia Esteves ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Defect ◽  
Asparagine Synthetase ◽  
Dried Blood Spot ◽  
Synthetase Deficiency ◽  
Whole Exome ◽  
Asparagine Synthetase Deficiency ◽  
Blood Spot

scholarly journals Using dried blood spot samples from a trio for linked-read whole-exome sequencing

2019 ◽  
Vol 27 (6) ◽  
pp. 980-988 ◽  
Author(s):  
Ólavur Mortensen ◽  
Leivur Nattestad Lydersen ◽  
Katrin Didriksen Apol ◽  
Guðrið Andorsdóttir ◽  
Bjarni á Steig ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Dried Blood Spot ◽  
Whole Exome ◽  
Blood Spot

scholarly journals DOCK8 mutation diagnosed using whole-exome sequencing of the dried blood spot-derived DNA: a case report of an Iraqi girl diagnosed in Japan

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Lika’a Fasih Y. Al-Kzayer ◽  
Hanadi Munaf H. Al-Aradi ◽  
Tomonari Shigemura ◽  
Kenji Sano ◽  
Miyuki Tanaka ◽  
...  
Keyword(s):  
Case Report ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Dried Blood Spot ◽  
Whole Exome ◽  
Blood Spot

scholarly journals Whole Exome Sequencing Is the Preferred Strategy to Identify the Genetic Defect in Patients With a Probable or Possible Mitochondrial Cause

2018 ◽  
Vol 9 ◽  
Author(s):  
Tom E. J. Theunissen ◽  
Minh Nguyen ◽  
Rick Kamps ◽  
Alexandra T. Hendrickx ◽  
Suzanne C. E. H. Sallevelt ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Defect ◽  
Whole Exome

scholarly journals Whole Exome Sequencing Identifies Three Novel Mutations in the ASPM Gene From Saudi Families Leading to Primary Microcephaly

2021 ◽  
Vol 8 ◽  
Author(s):  
Muhammad Imran Naseer ◽  
Angham Abdulrahman Abdulkareem ◽  
Osama Yousef Muthaffar ◽  
Sameera Sogaty ◽  
Hiba Alkhatabi ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Frameshift Mutation ◽  
Genetic Defect ◽  
Deletion Mutation ◽  
Primary Microcephaly ◽  
Novel Mutations ◽  
Whole Exome ◽  
Novel Variants ◽  
Healthy Control

Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental defect that is characterized by reduced head circumference at birth along with non-progressive intellectual disability. Till date, 25 genes related to MCPH have been reported so far in humans. The ASPM (abnormal spindle-like, microcephaly-associated) gene is among the most frequently mutated MCPH gene. We studied three different families having primary microcephaly from different regions of Saudi Arabia. Whole exome sequencing (WES) and Sanger sequencing were done to identify the genetic defect. Collectively, three novel variants were identified in the ASPM gene from three different primary microcephaly families. Family 1, showed a deletion mutation leading to a frameshift mutation c.1003del. (p.Val335*) in exon 3 of the ASPM gene and family 2, also showed deletion mutation leading to frameshift mutation c.1047del (p.Gln349Hisfs*18), while in family 3, we identified a missense mutation c.5623A>G leading to a change in protein (p.Lys1875Glu) in exon 18 of the ASPM gene underlying the disorder. The identified respective mutations were ruled out in 100 healthy control samples. In conclusion, we found three novel mutations in the ASPM gene in Saudi families that will help to establish a disease database for specified mutations in Saudi population and will further help to identify strategies to tackle primary microcephaly in the kingdom.

scholarly journals Whole Exome Sequencing Reveals Genetic Predisposition in a Large Family with Retinitis Pigmentosa

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Juan Wu ◽  
Lijia Chen ◽  
Oi Sin Tam ◽  
Xiu-Feng Huang ◽  
Chi-Pui Pang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Retinitis Pigmentosa ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Direct Sequencing ◽  
Genetic Defect ◽  
Chinese Family ◽  
Next Generation ◽  
Whole Exome ◽  
Generation Sequencing

Next-generation sequencing has become more widely used to reveal genetic defect in monogenic disorders. Retinitis pigmentosa (RP), the leading cause of hereditary blindness worldwide, has been attributed to more than 67 disease-causing genes. Due to the extreme genetic heterogeneity, using general molecular screening alone is inadequate for identifying genetic predispositions in susceptible individuals. In order to identify underlying mutation rapidly, we utilized next-generation sequencing in a four-generation Chinese family with RP. Two affected patients and an unaffected sibling were subjected to whole exome sequencing. Through bioinformatics analysis and direct sequencing confirmation, we identified p.R135W transition in the rhodopsin gene. The mutation was subsequently confirmed to cosegregate with the disease in the family. In this study, our results suggest that whole exome sequencing is a robust method in diagnosing familial hereditary disease.

scholarly journals Whole-exome sequencing gives additional benefits compared to candidate gene sequencing in the molecular diagnosis of children with growth hormone or IGF-1 insensitivity

2017 ◽  
Vol 177 (6) ◽  
pp. 485-501 ◽  
Author(s):  
Lucy Shapiro ◽  
Sumana Chatterjee ◽  
Dina G Ramadan ◽  
Kate M Davies ◽  
Martin O Savage ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Candidate Gene ◽  
Short Stature ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Genetic Defect ◽  
Significant Proportion ◽  
Genetic Diagnosis ◽  
Whole Exome

Background GH insensitivity (GHI) is characterised by short stature, IGF-1 deficiency and normal/elevated serum GH. IGF-1 insensitivity results in pre- and post-natal growth failure with normal/high IGF-1 levels. The prevalence of genetic defects is unknown. Objective To identify the underlying genetic diagnoses in a paediatric cohort with GH or IGF-1 insensitivity using candidate gene (CGS) and whole-exome sequencing (WES) and assess factors associated with the discovery of a genetic defect. Methods We undertook a prospective study of 132 patients with short stature and suspected GH or IGF-1 insensitivity referred to our centre for genetic analysis. 107 (96 GHI, 88 probands; 11 IGF-1 insensitivity, 9 probands) underwent CGS. WES was performed in those with no defined genetic aetiology following CGS. Results A genetic diagnosis was discovered 38/107 (36%) patients (32% probands) by CGS. WES revealed 11 patients with genetic variants in genes known to cause short stature. A further 2 patients had hypomethylation in the H19/IGF2 region or mUPD7 consistent with Silver–Russell Syndrome (total with genetic diagnosis 51/107, 48% or 41/97, 42% probands). WES also identified homozygous putative variants in FANCA and PHKB in 2 patients. Low height SDS and consanguinity were highly predictive for identifying a genetic defect. Conclusions Comprehensive genetic testing confirms the genetic heterogeneity of GH/IGF-1 insensitivity and successfully identified the genetic aetiology in a significant proportion of cases. WES is rapid and may isolate genetic variants that have been missed by traditional clinically driven genetic testing. This emphasises the benefits of specialist diagnostic centres.

scholarly journals Novel Immune Checkpoint Deficiency and Susceptibility to EBV-Associated Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2326-2326
Author(s):  
Ido Somekh ◽  
Thomas Magg ◽  
Alejandro Gallón Duque ◽  
Tali Stauber ◽  
Atar Lev ◽  
...  
Keyword(s):  
T Cells ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Immune Checkpoint ◽  
Conflicts Of Interest ◽  
Recombinant Expression ◽  
Genetic Defect ◽  
Primary Immune Deficiency ◽  
Genetic Rescue ◽  
Whole Exome

Background: Understanding genetic predisposition to cancer is of paramount importance to tailor therapeutic strategies. Several defects in immune checkpoint regulators have been discovered in patients with EBV-induced lymphoma (e.g. CD27, PRKCD, RASGRP1, MAGT1, SH2D1A, ITK). Here, we describe the clinical and immune phenotype of 2 unrelated patients from consanguineous families presenting with a primary immune deficiency (PID) and EBV-associated lymphoproliferation due to biallelic mutations in CD137 (TNFRSF9/4-1BB). Methods: One patient of Turkish origin (P1) and Palestinian origin (P2), respectively were evaluated. Genetic analysis using whole exome sequencing was conducted. Immunological and biochemical assays were performed on primary patient material. Results: Clinical findings included recurrent sinopulmonary and herpes virus infections from childhood on. One patient suffered from auto-immunity (AIHA and auto-immune thrombocytopenia). Abnormal immunoglobulin levels were documented (IgG 413-1670, IgM 105-714, IgA 49-68 mg/dL). Both patients developed EBV-associated lymphoproliferative disorders: P1 developed Burkitt lymphoma and was treated according to NHL-BFM2000 regimen in combination with rituximab. He is currently in remission. P2 had monoclonal EBV-positive lymphoproliferation and was successfully treated with immunosuppressive therapy (e.g. cellcept, glucocorticoids). To shed light on the underlying genetic etiology, we performed whole exome sequencing. A large homozygous deletion in CD137 (c.1_545+1716del) was identified for P1, while P2 harbored a homozygous missense mutation (c.C452T, p.Thr151Met). Impaired anti-CD3 T cell lymphocyte activation and proliferation were observed, amenable to correction upon addition of anti-CD28 monoclonal antibodies. In an attempt to provide definitive proof that the CD137 gene variant causes the activation defect of T-cells, we designed a genetic rescue experiment in patient T cells. Upon retrovirus-mediated recombinant expression of WT CD137, proliferation and activation defects in T cells were restored. Conclusions: In sum, we here show that a genetic defect in the immune checkpoint molecule CD137 causes a new primary immunodeficiency disorder with susceptibility to EBV-induced lymphomagenesis. Disclosures No relevant conflicts of interest to declare.

Whole Exome Sequencing (WES) in Familien mit linksventrikulärer Ausfluβtraktobstruktion (LVOTO)

2014 ◽  
Vol 62 (S 02) ◽  
Author(s):  
M. Hitz ◽  
S. Al-Turki ◽  
A. Schalinski ◽  
U. Bauer ◽  
T. Pickardt ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Whole Exome

FV 1031. Whole Exome Sequencing for Children with Dyskinetic Movement Disorder

2018 ◽  
Author(s):  
Yasemin Dincer ◽  
Michael Zech ◽  
Matias Wagner ◽  
Nikolai Jung ◽  
Volker Mall ◽  
...  
Keyword(s):  
Movement Disorder ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Whole Exome ◽  
Dyskinetic Movement
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