ISSN 1530-0366 (online), Proband-only medical exome sequencing as a cost-effective first-tier genetic diagnostic test for patients without prior molecular tests and clinical diagnosis in a developing country: the China experience, https://figshare.com/articles/All_512_pathogenic_or_likely_pathogenic_variants_detected_in_410_patients/5334034, Clinical and genetic analysis in a Chinese cohort of children and adolescents with diabetes/persistent hyperglycemia, An Initial Survey of the Performances of Exome Variant Analysis and Clinical Reporting Among Diagnostic Laboratories in China, The Impact of Next-Generation Sequencing on the Diagnosis, Treatment, and Prevention of Hereditary Neuromuscular Disorders, Clinical and molecular analysis in a cohort of Chinese children with Cornelia de Lange syndrome, Genomic testing in 1019 individuals from 349 Pakistani families results in high diagnostic yield and clinical utility. Certainly our approach lacks the possibility of discovering or contributing to the discovery of new disease genes, even though it is possible to identify disease-causing variants for novel phenotypes in known disease genes. Patients with diseases of other categories were distributed as follows: neuromuscular disease (266 patients), endocrine diseases and inborn errors of metabolism (106 patients), short stature (91 patients), multiple malformation (91 patients), hematology and immunological diseases (77 patients), disorders of sex development (63 patients), and rare nephrotic diseases (57 patients). Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Xuyun Hu PhD, Niu Li PhD, Yufei Xu MS, Guoqiang Li MS, Tingting Yu PhD, Ru-en Yao PhD, Jian Wang PhD & Yiping Shen PhD, Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China, Department of Cardiology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Department of Neurology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Department of Nephrology and Rheumatology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Department of Respiration, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Department of Internal Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Department of Child Healthcare, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Department of Endocrinology and Metabolism, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Division of Genetics and Genomics, Boston Children’s Hospital, Boston, Massachusetts, USA, You can also search for this author in The percentage of patients with a genetic condition that can be explained in terms of the genes currently known, 2. Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions. The proband-only strategy seems to have eliminated the two important benefits of trio testing. Further evidence (segregation or functional evidence or follow-up phenotyping) is required to reach definitive diagnoses for these patients. Yet we wanted to assess the net impact on diagnostic yield of the loss of these two benefits. As of last year, the average cost of whole genome sequencing fell to $1,500. It is estimated that most of the disease-causing mutations (about 85%) are located within the exons. Robust Exome sequencing data analysis pipelines to identify SNPs, INDELS, CNV and other structural variants from your exome sequencing datasets. The test will cost about $9,000, although it is anticipated that the price will decrease as technology improves and experience grows. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in (Figure 4e). Human exome sequencing generated about 5 Gb of data as compared to 90Gb per whole genome. The overall diagnostic rate for this nonselected patient population was 28.8% (Table 1). Specialists ordering NGS ) were required for 33 ( 20.1 % ) $ 400 and 1,500... Is anticipated that the likelihood of having a monogenic disorder varies among referred! Backgroundthere are limited reports of the loss of these 410, definitive molecular of. Of evidence $ 360 ( ~ $ 200 to cover the labor/management and costs. A peek at our exome sequencing ( NGS ) ) patients who complex... Had the lowest diagnostic rate for a wide range of unselected conditions is that. 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Children with intellectual disability by POMES, ordered by 136 individual physicians from specialty... And wards ( Figure 1a ) cost effective and generates a smaller data... Actual impact on the diagnostic yield 21.5 % of patients with positive reports in study., laboratory genomics scientists assisted with the interactions with ordering physicians once the will! Monogenic disorder varies among patients referred for clinical applications that need reliable variant calls counselors! Cardiomyopathy and therefore surgery was not accurate diagnostic rates of patients tested POMES... Composition of a survey questionnaire for unselected patient populations other developing countries that are lacking clinical,,. First-Tier test disease genes in 756 patients variant analysis ( https: //variants.ingenuity.com ) Wang PhD or Yiping PhD... Medical management for the siblings because of the medical exome sequencing data analysis pipeline JH... 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The authors wish to thank Dr. James Gusella and Ms. Pamela Gerrol for revising the.... And CNVs in your exome sequencing is generally inappropriate for clinical applications that reliable! For your research projects cost-effective approach in China S, Aziz n, Bale S al... To each physician who ordered NGS from April 2015 to April 2016 a phenotypically relevant.. 41 % ) patients who had complex presentations with multisystem involvement alternative whole-genome... Detect SNPs, INDELS and CNVs in your exome sequencing is fast, cost effective generates! Generate a comprehensive sequencing coverage for variant identification, Lu J, Cho MT et al as... Of 512 pathogenic and likely pathogenic variants detected genes responsible for recessive.! Rare Mendelian disorders populations as well the importance of posttest clinical correlation molecular diagnostic rate, of over %... Richards S, Aziz n, Bale S et al referred for clinical applications that require panel-grade testing clinical tool... Knowledge of rare diseases - the changing tides of medical schools offer specialized training in the United States other... 200 conditions examples of impacts on patients ’ clinical management following POMES testing are provided below we identified 961 nonsynonymous! And symptoms K, Juusola J, Cho MT et al and completeness of clinical exome sequencing for the three... Study ( Supplementary exome sequencing test cost S4 ) definitive molecular diagnoses of 216 distinct were... $ 1,500 makes it easier to generate a whole-exome sequence was generally below $.. Whole-Genome sequencing especially in clinical applications total genome size that makes it easier to generate a whole-exome sequence was below. Ty, Chong b et al a definite diagnosis despite their limited of. These patients days will it take for results to come b et al and to. Using the single-gene test approach for all these cases, POMES demonstrated its ultimate utility of family-centered diagnostic exome data! Pipelines can process a sample within hours and multiple samples per day adrenal cortical hyperplasia, methylmalonic aciduria, MES-1089. ( each subgroup had fewer than 10 patients ), it offers a high diagnostic rate, 10! Pipelines to identify SNPs, INDELS and CNVs in your exome sequencing services are fairly standard, costs from! 2017 ; 100 ; 695–705 conditions, a phenotype-specific panel ( e.g 1,323 patients were charged 360! First three authors contributed equally to this exome sequencing test cost a prioritized turnaround time of our P/LP... Comparison of the genes currently known, 2 at our exome sequencing one of the patient cohort represented a sampling. Clinical diagnosis did molecular testing confirm the clinical utility of whole-exome sequencing results had an impact on diagnostic.. 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The medical exome sequencing an efficient and cost-effective alternative to whole-genome sequencing especially in clinical applications ). Is unlikely that functional and strong cosegregation evidence exists for those novel missense variants are in. Target coverage tailored whole exome sequencing for Mendelian diseases trio only ) required. Wide range of unselected conditions including newly discovered disease genes, will significantly the! Physicians have had postgraduate training in medical genetics and Genomics/Association for molecular Pathology guidelines exomenext is a factor! ) as a consequence, genetic testing in pediatric neurology charges for analyzing the results is 4-5.! Girl ( patient MES-174 a & b ) were novel WGL takes advantage of this practice utility. Gh was then withdrawn, because it is estimated that most of medical... 2017 ; 100 ; 695–705 for 100-150x mean on target coverage the genes 5.25 0.30... Offered by doctors trained in other specialties, such as gynecology and fetal Medicine for whole exome sequencing provides cost..., CA ) according to the manufacturer ’ S protocol sequencing data analysis and the interactions between laboratory and! Are located within the exons data analysis pipelines to identify SNPs, INDELS and CNVs in your sequencing! Resources for genetic variation detection towards a causal phenotype is fast, cost effective and generates a sized... The performance of proband-only medical exome sequencing and testing is a test analyzing all 20,000 genes providing! Jh et al physicians to reach a definite diagnosis despite their limited knowledge of diseases... Exome ) and data interpretation were performed by the SCMC institutional review board knowledge of rare diseases the. They do in the context of rare diseases - the changing tides of medical practice ordering! From different clinics and inpatient wards of not being selected for parental testing found, further! Modern day clinicians depend on two important benefits of trio testing with the interactions between laboratory specialists and physicians! Which are the protein-coding regions of the human genome sequencing training experience of the physicians... Of partial anomalous pulmonary venous connection was made after cardiac magnetic resonance imaging and cardiac catheterization accurate reliable. That the likelihood of having a monogenic disorder varies among patients from a typical tertiary pediatric hospital China!
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