scholarly journals Phenotypic signatures in clinical data enable systematic identification of patients for genetic testing

2020 ◽  
Author(s):  
Theodore J Morley ◽  
Lide Han ◽  
Jonathan Morra ◽  
Nancy J Cox ◽  
Lisa Bastarache ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Clinical Data ◽  
Genetic Disease ◽  
Genetic Test ◽  
Genetic Diseases ◽  
Copy Number Variant ◽  
Test Sample ◽  
Chromosomal Microarray ◽  
Quickest Path ◽  
Organ Systems

Around five percent of the population is affected by a rare disease, most often due to genetic variation. A genetic test is the quickest path to a diagnosis, yet most suffer through years of diagnostic odyssey before getting a test, if they receive one at all. Identifying patients that are likely to have a genetic disease and therefore need genetic testing is paramount to improving diagnosis and treatment. While there are thousands of previously described genetic diseases with specific phenotypic presentations, a common feature among them is the presence of multiple rare phenotypes which often span organ systems. Here, we hypothesize that these patients can be identified from longitudinal clinical data in the electronic health record (EHR). We used diagnostic information from the EHRs of 2,286 patients that received a chromosomal microarray and 9,144 matched controls to train and test a prediction model. We identified high prediction accuracy (AUROC = 0.97, AUPR = 0.92) in a held-out test sample and in 172,265 hospital patients where cases were defined broadly as interacting with a genetics provider (AUROC = 0.9, AUPR = 0.63). High probabilities (median = 0.97) were associated with 46 patients carrying a known pathogenic copy number variant (CNV) among a subset of 6,445 genotyped patients. Our model identified many more patients needing a genetic test while increasing the proportion having a putative genetic disease compared to the current nonsytematic approach. Taken together, we demonstrate that phenotypic patterns representative of a genetic disease can be captured from EHR data and provide an opportunity to systematize decision making on genetic testing to speed up diagnosis, improve care, and reduce costs.

scholarly journals The diagnostic trajectory of infants and children with clinical features of genetic disease

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Brock E. Schroeder ◽  
Nina Gonzaludo ◽  
Katie Everson ◽  
Kyi-Sin Than ◽  
Jeff Sullivan ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Clinical Features ◽  
Genetic Disease ◽  
Pediatric Patients ◽  
Genetic Disorders ◽  
Genetic Diseases ◽  
Cost Of Care ◽  
Clinical Indicators ◽  
Utilization Of Services ◽  
Number Of Patients

AbstractWe characterized US pediatric patients with clinical indicators of genetic diseases, focusing on the burden of disease, utilization of genetic testing, and cost of care. Curated lists of diagnosis, procedure, and billing codes were used to identify patients with clinical indicators of genetic disease in healthcare claims from Optum’s de-identified Clinformatics® Database (13,076,038 unique patients). Distinct cohorts were defined to represent permissive and conservative estimates of the number of patients. Clinical phenotypes suggestive of genetic diseases were observed in up to 9.4% of pediatric patients and up to 44.7% of critically-ill infants. Compared with controls, patients with indicators of genetic diseases had higher utilization of services (e.g., mean NICU length of stay of 31.6d in a cohort defined by multiple congenital anomalies or neurological presentations compared with 10.1d for patients in the control population (P < 0.001)) and higher overall costs. Very few patients received any genetic testing (4.2–8.4% depending on cohort criteria). These results highlight the substantial proportion of the population with clinical features associated with genetic disorders and underutilization of genetic testing in these populations.

scholarly journals Chromosomal Microarray Analysis as First-Tier Genetic Test for Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Chia-Hsiang Chen ◽  
Min-Chih Cheng ◽  
Tsung-Ming Hu ◽  
Lieh-Yung Ping
Keyword(s):  
Genetic Testing ◽  
Microarray Analysis ◽  
Copy Number ◽  
Genetic Test ◽  
Molecular Genetic ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Clinical Settings ◽  
Schizophrenia Spectrum ◽  
Spectrum Disorders

Schizophrenia is a chronic, devastating mental disorder with complex genetic components. Given the advancements in the molecular genetic research of schizophrenia in recent years, there is still a lack of genetic tests that can be used in clinical settings. Chromosomal microarray analysis (CMA) has been used as first-tier genetic testing for congenital abnormalities, developmental delay, and autism spectrum disorders. This study attempted to gain some experience in applying chromosomal microarray analysis as a first-tier genetic test for patients with schizophrenia. We consecutively enrolled patients with schizophrenia spectrum disorder from a clinical setting and conducted genome-wide copy number variation (CNV) analysis using a chromosomal microarray platform. We followed the 2020 “Technical Standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)” to interpret the clinical significance of CNVs detected from patients. We recruited a total of 60 patients (36 females and 24 males) into this study. We detected three pathogenic CNVs and one likely pathogenic CNV in four patients, respectively. The detection rate was 6.7% (4/60, 95% CI: 0.004–0.13), comparable with previous studies in the literature. Also, we detected thirteen CNVs classified as uncertain clinical significance in nine patients. Detecting these CNVs can help establish the molecular genetic diagnosis of schizophrenia patients and provide helpful information for genetic counseling and clinical management. Also, it can increase our understanding of the pathogenesis of schizophrenia. Hence, we suggest CMA is a valuable genetic tool and considered first-tier genetic testing for schizophrenia spectrum disorders in clinical settings.

scholarly journals Single-cell Sequencing-based Pre-implantation Genetic Testing-M (PGT-M) of the Heterozygous Mutations of PKD1 Gene

2020 ◽  
Author(s):  
Na Li ◽  
Cong Xiu Miao ◽  
HuiLing Bi ◽  
Hui Miao ◽  
Dan Li ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Single Cell ◽  
Sanger Sequencing ◽  
Genetic Diseases ◽  
Copy Number Variant ◽  
Final Diagnosis ◽  
Mutation Site ◽  
Single Cell Sequencing ◽  
Pkd1 Gene ◽  
Important Approach

Abstract Objectives: Polycystic kidney disease (PKD) is a common autosomal monogenic genetic disease. PKD1 mutation accounts for about 85% of ADPKD patients. Pre-implantation genetic testing-M (PGT-M for monogenic) is an important approach to prevent the transmission of genetic diseases from parents to the offspring. Design: In this study, We have identified the family linkage and mutation site in embryos with NGS-based SNP phasing and Sanger Sequencing.Methods: Multiple Annealing and Looping Based Amplification Cycles (MALBAC) method was employed to amplify the whole genome of trophoblast cells. Copy Number Variant (CNV), and single nucleotide polymorphism (SNP) were used to assess the embryo state. Results: In the eight embryos, Embryo 02 and Embryo 04 were removed from further analysis because of the Multiple chromosomes abnormal (2 of 8, 25%). Embryo 05, Embryo 06, Embryo 07, and Embryo 08 were judged as 46,XN,-15q(q23→qter,~31M,×1,mos*), 45,XN,-16(×1), 47,XN,+2(×3),-7p(pter→p14.3,~35M,×1,mos*), and 46,XN, +16(×3,mos*),-20p(pter→p11.23,~23M,×1,mos*),+22(×3,mos*), respectively (4 of 8, 50%). Meanwhile, Embryo 01 and Embryo 03 were judged as 46, XN (2 of 8, 25%). The results of SNP phasing and Sanger Sequencing suggested that Embryo 01 and Embryo 05 had none of PKD1 gene mutation. Limitations: Up to now, PGT-M is complicated and expensive. Meanwhile, PGT-M obtains the final diagnosis through invasive manipulation of embryos, which may bring adverse effects on offspringConclusion: NGS-based single-cell sequencing combined with CNV, Sanger Sequencing, and SNP phasing is a reliable testing system for PGT-M application. This work presented here would provide a detailed understanding of the NGS-based single-cell sequencing application in ADPKD.

Genetic Disorders in the Fetus from Diagnosis to Treatment

2020 ◽  
Author(s):  
Tayebeh Rabaninia ◽  
Nooshin Amjadi
Keyword(s):  
Mental Illness ◽  
Heart Disease ◽  
Genetic Counseling ◽  
Genetic Testing ◽  
Genetic Disease ◽  
Genetic Disorders ◽  
Genetic Diseases ◽  
Medical Knowledge ◽  
Gene Mutations ◽  
Prevention Of Disability

Background: Today there are many diseases that genetics contributes to these, including diabetes, hypertension, cancer, heart disease, various types of cancers and even mental illness, and by the advancement of medical knowledge The number of genetic diseases is increasing now. most people think about genetic diseases as inherited diseases, which are mostly caused by gene mutations and other genetically inherited factors. Most of the genetic disorders currently do not have 100% treatment, and the only way is to preventing the prevalence of them before marriage.   Methods: Eligible articles were identified by search of databases including NCBI, PubMed, ISI Web of Knowledge and Google scholar up to July 2017.   Results: In the field of prevention of disability and genetic disorders, many members who are at risk of genetic disease should have genetic counseling to get useful information about it. Without genetic counseling, genetic testing is meaningless, as people do not go to the laboratory without a doctor's visit; Genetic counselors won’t be able to stop people from getting married, but they provide solutions to prevent them from possible disorders.   Conclusions: This study provides information on genetic diseases and prevents them in newborns and suggests new solutions for the treatment of these diseases.

scholarly journals First French study relative to preconception genetic testing: 1500 general population participants’ opinion

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Valérie Bonneau ◽  
Mathilde Nizon ◽  
Xenia Latypova ◽  
Aurélie Gaultier ◽  
Eugénie Hoarau ◽  
...  
Keyword(s):  
Genetic Testing ◽  
General Population ◽  
Social Security ◽  
Genetic Disease ◽  
Ethical Issues ◽  
Family Doctor ◽  
Screening Strategy ◽  
Medical Prescription ◽  
Medical Progress ◽  
Increased Risk

Abstract Background Until very recently, preconception genetic testing was only conducted in particular communities, ethnic groups or families for which an increased risk of genetic disease was identified. To detect in general population a risk for a couple to have a child affected by a rare, recessive or X-linked, genetic disease, carrier screening is proposed in several countries. We aimed to determine the current public opinion relative to this approach in France, using either a printed or web-based questionnaire. Results Among the 1568 participants, 91% are favorable to preconception genetic tests and 57% declare to be willing to have the screening if the latter is available. A medical prescription by a family doctor or a gynecologist would be the best way to propose the test for 73%, with a reimbursement from the social security insurance. However, 19% declare not to be willing to use the test because of their ethic or moral convictions, and the fear that the outcome would question the pregnancy. Otherwise, most participants consider that the test is a medical progress despite the risk of an increased medicalization of the pregnancy. Conclusion This first study in France highlights a global favorable opinion for the preconception genetic carrier testing under a medical prescription and a reimbursement by social security insurance. Our results emphasize as well the complex concerns underpinned by the use of this screening strategy. Therefore, the ethical issues related to these tests include the risk of eugenic drift mentioned by more than half of the participants.

High prevalence of familial and genetic disease in children with cardiomyopathies: baseline paediatric data from the ESC EORP Cardiomyopathy and Myocarditis registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.P Kaski ◽  
A.G Maggioni ◽  
P Charron ◽  
P.M Elliott ◽  
J.R Gimeno ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Genetic Disease ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Neuromuscular Disorders ◽  
High Yield ◽  
Causative Mutation ◽  
Inborn Errors ◽  
Male Predominance ◽  
Familial Disease ◽  
Significant Difference

Abstract Background Previous studies on paediatric cardiomyopathies have provided useful information on their epidemiology and clinical presentation but have been limited by a lack of detailed data on genetic testing and aetiology. Purpose The purpose of this study was to examine the frequency of familial and genetic disease among children with cardiomyopathy enrolled in the European Society of Cardiology (ESC) Cardiomyopathy and Myocarditis EORP Long-Term Registry (CMY-LT). Methods 633 individuals aged &lt;18 years with hypertrophic cardiomyopathy [HCM; n=387 (61%)], dilated cardiomyopathy (DCM; n=205 (33%)], restrictive cardiomyopathy [RCM; n=28 (4%)] and arrhythmogenic right ventricular cardiomyopathy [ARVC; n=11 (2%)] were enrolled by 26 centres from 14 countries. Mean age at diagnosis was 5.2 (±5.4) years and there was a male predominance [n=372 (59%)] across all cardiomyopathy subtypes, with the exception of DCM in those diagnosed &lt;10 years of age (p=0.005). 541 (87%) were probands compared to 83 (13%) first-degree relatives. Results Overall, 253 patients (47% of those reported) had familial disease; in those diagnosed between 10 and 18 years of age, familial disease was most frequent in HCM and least frequent in DCM [57 (55%) vs 12 (32%); p=0.046]. Genetic testing was performed in 414 (68%) patients. In those diagnosed &lt;10 years, genetic testing was more frequently performed in HCM [128 (67%) vs 33 (37%) in DCM, 10 (56%) in RCM and 1 (50%) in ARVC; p=0.008]; in those aged 10–18, genetic testing was most frequent in ARVC [n=8 (89%)] followed by HCM [n=81 (69%)], RCM [n=1 (50%)] and DCM [n=22 (46%); p=0.007]. A causative mutation was reported in 250 patients (60%), with a higher yield in those aged 10–18 vs &lt;10 years [77 (69%) vs 172 (57%), p=0.032]. In those &lt;10 years, the prevalence of reported causative mutations was highest in HCM [128 (67%) vs 10 (56%) in RCM, 1 (50%) in ARVC and 33 (37%) in DCM; p&lt;0.001]; in those 10–18 years, there was no significant difference in prevalence of reported causative variants between cardiomyopathy subtypes. Rare disease phenocopies were reported in 171 patients (27%): malformation syndromes [n=75 (12%)]; neuromuscular disorders [n=49 (8%)]; inborn errors of metabolism [n=20 (3%)]; mitochondrial [n=18 (3%)]; and chromosomal [n=15 (2%)]. Phenocopies were reported most frequently in patients &lt;10 years [135 (30%) vs 35 (20%) in those aged 10–18 years; p=0.008], particularly in HCM in those &lt;10 years [n=110 (41%); p&lt;0.001 vs other subtypes] and DCM in those aged 10–18 years [n=18 (38%); p=0.03 vs other subtypes]. Conclusion This study confirms the heterogeneous aetiology of childhood cardiomyopathies and demonstrate a higher prevalence of familial disease than previously reported in paediatric populations. Genetic testing is performed in a high proportion of patients, with a high yield of reported causative variants. Funding Acknowledgement Type of funding source: None

Cancer specialists in the VA as early adopters of clinical genetic services.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11029-11029
Author(s):  
Maren Theresa Scheuner ◽  
Paloma Sales ◽  
Mary Whooley ◽  
Katherine Hoggatt ◽  
Michael Kelley
Keyword(s):  
Risk Assessment ◽  
Genetic Testing ◽  
Genetic Test ◽  
Primary Care Providers ◽  
Precision Oncology ◽  
Genetic Tests ◽  
The Past ◽  
Cancer Specialists ◽  
Genetics Referral ◽  
Test Ordering

11029 Background: Genetic testing has become essential to delivery of cancer treatment, risk assessment, surveillance, and prevention. We sought to understand the use of genetic tests by clinicians in the Department of Veterans Affairs (VA). Methods: We administered a web-based survey to clinicians at 20 VA facilities with precision oncology programs. We excluded respondents if they were: not at one of the 20 VA facilities; not seeing patients in VA; not a physician, nurse practitioner (NP), physician assistant (PA), or pharmacist; a medical geneticist or specialty was not reported; or if the survey was incomplete. Using multiple logistic regression, we assessed the association between genetic test ordering, genetics referral, and clinician characteristics. Results: There were 909 (909/11,442, 8%) eligible respondents with 61% women and 64% under age 55. There were 571 physicians (63%), 200 NPs (22%), 93 pharmacists (10%), and 45 PAs 5(%). There were 361 (40%) primary care providers (PCPs), 90 (10%) cancer specialists, and 458 (50%) non-cancer specialists. Only 21% of clinicians reported feeling prepared to use genetic tests in their practice. In the past year, only 8% had ordered at least one multi-gene cancer test (germline, tumor or both), 12% a pharmacogenetic test, and 0.2%, an exome. Compared to physicians, NPs were 60% less likely (OR = 0.42, 0.23-0.77, p = 0.005), pharmacists, 80% less likely (OR = 0.22, 0.08-0.62, p = 0.005), and PAs, 90% less likely (OR = 0.08, 0.01-0.58, p = 0.01) to have ordered a genetic test. Compared to PCPs, cancer specialists were almost 5 times more likely to order a genetic test (OR = 4.74, 2.57-8.73, p < 0.0001); there was no difference in genetic test ordering between PCPs and non-cancer specialists. Among clinicians (n = 72) who had ordered cancer genetic tests, only about two-thirds were confident in knowing the indications for testing; discussing the potential benefits, harms and limitations of testing; understanding the test report; and knowing implications of results on disease management and prevention. Clinicians (n = 106) who had ordered pharmacogenetic tests had lower frequencies of confidence in these tasks. About half (52%) of the cancer specialists had referred patients to genetics in the past year; they were 1.8 times more likely than PCPs to refer (OR = 1.82, 1.10-3.03, p = 0.02), and non-cancer specialists were about 50% less likely than PCPs to refer (OR = 0.46, 0.33-0.64, p < 0.0001). Conclusions: In the VA, cancer specialists are integrating genetic testing and genetics referral into their practice more than PCPs and other specialists. However, genetic testing is underutilized, and many clinicians remain unprepared to use genetic tests in their practice. These results will inform workforce planning, clinician education, and development of clinical decision support to facilitate genetic risk assessment, informed consent, and ordering of genetic tests.

scholarly journals Genetic Basis of Male Infertility

2013 ◽  
Vol 4 (1) ◽  
pp. 37-39 ◽  
Author(s):  
Mosammat Rashida Begum ◽  
Mariya Ehsan
Keyword(s):  
Genetic Testing ◽  
Male Infertility ◽  
Medical Treatment ◽  
Intracytoplasmic Sperm Injection ◽  
Chromosomal Abnormality ◽  
Genetic Disease ◽  
Genetic Basis ◽  
Common Cause ◽  
Near Future ◽  
Spermatogenic Failure

Infertility is a couple's problem. Almost 50% case males are responsible for infertility. Most common cause is oligospermia and azoospermia and approximately 5% to 15% of men with azoospermia and severe oligospermia may have a chromosomal abnormality. Men with significant spermatogenic compromise are the candidates of intracytoplasmic sperm injection (ICSI). Raised FSH level above 9 is an indication of spermatogenic compromise. So, medical treatment for these patients is waste of time and money. Early attempt of assisted reproduction is ideal to avoid the crisis of total spermatogenic failure in near future. But before going for ICSI genetic testing if possible and proper counseling about possibilities of transmission of genetic disease to offspring is necessary. DOI: http://dx.doi.org/10.3329/akmmcj.v4i1.13683 AKMMC J 2013: 4(1): 37-39  

Sign in / Sign up

Export Citation Format

Share Document