Gene Testing
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2022 ◽  
Vol 42 (2) ◽  
pp. 296-297
Na-Kyoung Kim ◽  
Jong-Won Kim

2021 ◽  
Vol 22 (19) ◽  
pp. 10375
Clara Xiol ◽  
Maria Heredia ◽  
Ainhoa Pascual-Alonso ◽  
Alfonso Oyarzabal ◽  
Judith Armstrong

Rett syndrome (RTT) is a severe neurodevelopmental disorder that constitutes the second most common cause of intellectual disability in females worldwide. In the past few years, the advancements in genetic diagnosis brought by next generation sequencing (NGS), have made it possible to identify more than 90 causative genes for RTT and significantly overlapping phenotypes (RTT spectrum disorders). Therefore, the clinical entity known as RTT is evolving towards a spectrum of overlapping phenotypes with great genetic heterogeneity. Hence, simultaneous multiple gene testing and thorough phenotypic characterization are mandatory to achieve a fast and accurate genetic diagnosis. In this review, we revise the evolution of the diagnostic process of RTT spectrum disorders in the past decades, and we discuss the effectiveness of state-of-the-art genetic testing options, such as clinical exome sequencing and whole exome sequencing. Moreover, we introduce recent technological advancements that will very soon contribute to the increase in diagnostic yield in patients with RTT spectrum disorders. Techniques such as whole genome sequencing, integration of data from several “omics”, and mosaicism assessment will provide the tools for the detection and interpretation of genomic variants that will not only increase the diagnostic yield but also widen knowledge about the pathophysiology of these disorders.

Steven Toh ◽  
Chean Chung Shen

Chronic relapsing inflammatory optic neuropathy (CRION) is a recently described form of recurrent isolated subacute optic neuropathy, with accumulating evidence that it is a nosological distinct entity. The condition is highly responsive to systemic steroid treatment and prone to relapse on steroid withdrawal. Diagnosis and management of this condition is often challenging. This 33-year-old lady with family history of multiple sclerosis (MS), with uniocular visual loss of her right eye since 2 years old without apparent cause, presented with reduction of vision and loss of colour vision in the left eye, associated with painful eye movement. There was internuclear ophthalmoplegia but slit lamp examination were unremarkable. She had no other related sensory or motor symptoms. Magnetic resonance imaging (MRI) did not reveal any features of MS. Aquaporin-4 antibody, anti-MOG and gene testing for Leber’s hereditary optic neuropathy were all negative. Metabolic, infective, and other autoimmune causes were also excluded. Visual evoked potential studies of left eye showed a mild reduction in amplitude with no prolongation of latency. Her multiple optic neuritis recurrences were treated with intravenous steroids followed by tapering regime of oral prednisolone with good effect. Knowledge of this rare condition as part of the differential diagnoses of possible aetiologies of optic neuropathy is important among Ophthalmologists, as prompt diagnosis and steroid treatment helped reduce the associated risk of blindness. Multiple relapses after initial successful treatment of inflammatory optic neuropathy should raise the suspicion of CRION.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S19

2021 ◽  
pp. 598-604
Hung T. Tran ◽  
Khang V. Nguyen ◽  
Laurent Vercueil

Paroxysmal kinesigenic dyskinesia (PKD) is a rare condition characterized by abnormal involuntary movements that are precipitated by a sudden movement. PKD is often misdiagnosed with psychogenic movement disorders. Carbamazepine is usually the first choice of medication due to its well-established evidence but could induce Stevens-Johnson syndrome. We report a 21-year-old male patient with PKD referred to our movement disorders clinic after being misdiagnosed with conversion syndrome. PRRT2 gene testing using next-generation sequencing revealed a mutation in c.649dupC p. (Arg217fs). The patient responded well to carbamazepine but had to withdraw the treatment due to carbamazepine-induced Stevens-Johnson syndrome after 3 weeks of medication. Our patient did not respond to trials of levetiracetam and phenytoin but finally responded well to oxcarbazepine. The patient was followed up for 4 years, during which he had no attacks and no side effects. Here, we present a PKD case with carbamazepine-induced Stevens-Johnson syndrome successfully treated with oxcarbazepine despite the risk of cross-reactive skin eruption between these antiepileptics. Careful history taking and examining patient’s attacks are crucial to accurate diagnosis and treatment in PKD patients.

2021 ◽  
Masato Maekawa ◽  
Terumi Taniguchi ◽  
Kazuto Nishio ◽  
Kazuko Sakai ◽  
Kazuyuki Matsushita ◽  

Abstract To implement precision oncology, analytical validity as well as clinical validity and utility are important. However, proficiency testing (PT) to assess validity has not yet been systematically performed in Japan. To investigate the quality of next-generation sequencing (NGS) platforms and cancer genome testing prevalent in laboratories, we performed pilot PT using patient samples. We prepared 5 samples from patients with lung or colorectal cancer, extracted genomic DNA from the cancer tissue and peripheral blood, and distributed these to 15 laboratories. Most participating laboratories successfully identified the pathogenic variants, except for two closely located KRAS variants, and 25-bp delins in the EGFR exon 19, not identified by the in vitro diagnostics testing. Conversely, the EGFR L858R variant was successfully identified, and the allele frequency was similar for all the laboratories. A high DNA integrity number led to excellent depth and reliable NGS results. All NGS platforms and bioinformatics pipelines have advantages and disadvantages. We propose the use of a PT program using patient samples to ascertain the quality status of cancer gene testing in laboratories and to ensure that laboratories have sufficient information to develop advancements in precision medicine for cancer.

2021 ◽  
Vol 12 ◽  
Mays Altaraihi ◽  
Thomas van Overeem Hansen ◽  
Eric Santoni-Rugiu ◽  
Maria Rossing ◽  
Åse Krogh Rasmussen ◽  

IntroductionDICER1 syndrome encompasses a variety of benign and malignant manifestations including multinodular goitre, which is the most common manifestation among individuals carrying pathogenic DICER1 variants. This is the first study estimating the prevalence of pathogenic DICER1 variants in young individuals with multinodular goitre.MethodsDanish individuals diagnosed with nodular goitre based on thyroidectomy samples in 2001-2016 with the age limit at time of operation being ≤ 25 years were offered germline DICER1 gene testing.ResultsSix of 46 individuals, 13% (CI [3.3;22.7], p <0.05), diagnosed with nodular goitre on the basis of thyroidectomy samples under the age of 25 years had pathogenic germline variants in DICER1. They were found in different pathoanatomical nodular goitre cohorts i.e. nodular goitre (n=2), colloid nodular goitre (n=3) and hyperplastic nodular goitre (n=1).ConclusionsWe recommend referral of patients thyroidectomised due to goitre aged <21 years and patients thyroidectomised due to goitre aged <25 years with a family history of goitre to genetic counselling. Patients of all ages thyroidectomised due to goitre, who are affected by another DICER1 manifestation should be referred to genetic counselling.

2021 ◽  
Vol 10 (3) ◽  
pp. e001538
Emma White ◽  
Nathan Proudlove ◽  
Delordson Kallon

Among other tests, Barts Health NHS Trust clinical transplantation laboratory conducts two important gene-detection tests: human leucocyte antigen (HLA)-B*27 (‘B27’, associated with the diagnosis of ankylosing spondylitis) and HLA-B*57:01 (‘B57’, associated with prediction of abacavir hypersensitivity disorder). The turnaround time (TaT) from sample receipt to return of results is important to clinicians and their patients but was not monitored. Furthermore, we anticipated an imminent increase in demand from a forthcoming pathology service merger, together with long-term increases with the rise of personalised genetic medicine.In this quality improvement project, we identified current TaT performance and sources of delay. Over three plan-do-study-act (PDSA) cycles, we tested three change ideas, two involving using IT to remove manual administrative steps and alert us to samples needing progressing; both were retained. The other change involved separating out the targeted tests; we judged this not worthwhile with current demand levels, although something to be re-examined when volumes increase. During the project, we reduced mean TaT from 3.8 to 3.3 days and increased the proportion within our 5-day target from 78% to 100%. These have been sustained (at 3.4 days and 97%) for the 3 months following our PDSA cycles and illustrate that reducing variation can be as impactful as reducing the mean.We conducted this project during the COVID-19 disruption, which reduced demand substantially. We took advantage of this to allow staff to spend time on these improvement activities. Another interesting feature of the work is that during the project, we compared changes in performance on our targeted B27/B57 tests with that on another comparable test as a control, to consider the impact of the general increased attention (the Hawthorne effect). We found that performance on this control also increased comparably, but then fell away after our project finished, while it did not for B27/B57.

2021 ◽  
Vol 28 (5) ◽  
pp. 3268-3279
Maisam Makarem ◽  
Doreen A. Ezeife ◽  
Adam C. Smith ◽  
Janice J. N. Li ◽  
Jennifer H. Law ◽  

ROS1 rearrangements are identified in 1–2% of lung adenocarcinoma cases, and reflex testing is guideline-recommended. We developed a decision model for population-based ROS1 testing from a Canadian public healthcare perspective to determine the strategy that optimized detection of true-positive (TP) cases while minimizing costs and turnaround time (TAT). Eight diagnostic strategies were compared, including reflex single gene testing via immunohistochemistry (IHC) screening, fluorescence in-situ hybridization (FISH), next-generation sequencing (NGS), and biomarker-informed (EGFR/ALK/KRAS wildtype) testing initiated by pathologists and clinician-initiated strategies. Reflex IHC screening with FISH confirmation of positive cases yielded the best results for TAT, TP detection rate, and cost. IHC screening saved CAD 1,000,000 versus reflex FISH testing. NGS was the costliest reflex strategy. Biomarker-informed testing was cost-efficient but delayed TAT. Clinician-initiated testing was the least costly but resulted in long TAT and missed TP cases, highlighting the importance of reflex testing. Thus, reflex IHC screening for ROS1 with FISH confirmation provides a cost-efficient strategy with short TAT and maximizes the number of TP cases detected.

2021 ◽  
Jai N Patel ◽  
Danielle Boselli ◽  
James Symanowski ◽  
Stephanie Wodarski ◽  
ShRhonda Turner ◽  

Aim: We evaluated the application and clinical impact of multi-gene pharmacogenetic testing in oncology palliative medicine. Patients & Methods: In a single-arm pilot trial, cancer patients with uncontrolled pain were assessed in a palliative medicine clinic at baseline and received pharmacogenetic testing. Results were used as applicable up to the final visit (day 30). Pain scores, opioid prescribing, and use of pharmacogenetic test results were collected. Results: In 75 patients, the median baseline pain score was 7/10. Of 54 evaluable at the final visit, 28 required opioid modifications and 19 had actionable genotypes, mostly CYP2D6. Pain improvement (≥2-point reduction) was higher than historical data (56 vs 30%; p < 0.001). There were no differences in pain improvement between those with and without actionable genotypes (61 vs 53%). Conclusion: Multi-gene testing identified actionable genotypes and may improve cancer pain.

2021 ◽  
Vol 8 ◽  
Ziguan Zhang ◽  
Hongwei Chen ◽  
Wenbo Chen ◽  
Zhenghao Zhang ◽  
Runjing Li ◽  

Objective: To investigate the genetic characteristics and transcriptional regulation of the SCN5A gene of Brugada syndrome (BrS) patients in China.Methods: Using PubMed, Medline, China National Knowledge Internet (CNKI), and Wanfang Database, Chinese patients with BrS who underwent SCN5A gene testing were studied.Results: A total of 27 suitable studies involving Chinese BrS patients who underwent the SCN5A gene test were included. A total of 55 SCN5A gene mutations/variations were reported in Chinese BrS patients, including 10 from southern China and 45 from northern China. Mutations/variations of BrS patients from southern China mostly occurred in the regions of the α-subunit of Nav1.5, including DIII (Domain III), DIV, DIII-DIV, C-terminus regions, and the 3'UTR region. Furthermore, we analyzed the post-transcriptional modifications (PTMs) throughout the Nav1.5 protein encoded by SCN5A and found that the PTM changes happened in 72.7% of BrS patients from southern China and 26.7% from northern China.Conclusions: SCN5A mutations/variations of BrS patients in southern China mostly occurred in the DIII-DIV to C-terminus region and the 3'-UTR region of the SCN5A gene, different from northern China. PTM changes were consistent with the mutation/variation distribution of SCN5A, which might be involved in the regulation of the pathogenesis of BrS patients.

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