DNA-based carrier screening in primary healthcare: screening for aspartylglucosaminuria mutations in maternity health offices

Abstract Large-scale genetic screening programs are complex enterprises in which ethical, technical, medical, and socioeconomic aspects have to be handled with professional expertise. Establishment of automated, relatively robust, and inexpensive laboratory techniques is one step of this path. Here a pilot carrier-screening program for the mutations causing aspartylglucosaminuria was carried out for pregnant women in primary care maternity health offices. Women (1975) were tested before their 12th week of pregnancy, and 31 heterozygotes were detected. The sampling was based on dried blood strips, facilitating convenient handling and inexpensive mailing to the laboratory. The mutation detection technique, solid-phase mini-sequencing simplified by the use of scintillation microplates and automated equipment, proved to be rapid, simple, inexpensive, and reliable, with a low repeat rate (2.5%). In conclusion, we found that good collaboration between the primary healthcare unit, the laboratory, and counseling experts, combined with modern laboratory technology, facilitate reliable low-cost genetic testing.

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One-step synthesis and assembly of spindle-shaped akaganéite nanoparticles via sonochemistry

CrystEngComm ◽

10.1039/c8ce00470f ◽

2018 ◽

Vol 20 (21) ◽

pp. 2989-2995 ◽

Cited By ~ 2

Author(s):

Weikun Chen ◽

Pinqiang Dai ◽

Chunfu Hong ◽

Chan Zheng ◽

Weiguo Wang ◽

...

Keyword(s):

Large Scale ◽

Low Cost ◽

Scale Production ◽

Green Method ◽

Large Scale Production ◽

One Step

We demonstrate a green method based on sonochemistry for large-scale production of akaganéite nanoparticles and assemblies in low cost.

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Massive Multiplexing Can Deliver a $1 Test for COVID-19

10.1101/2020.05.05.079400 ◽

2020 ◽

Cited By ~ 2

Author(s):

Paul DN Hebert ◽

Sean WJ Prosser ◽

Natalia V Ivanova ◽

Evgeny V Zakharov ◽

Sujeevan Ratnasingham

Keyword(s):

Large Scale ◽

Low Cost ◽

Rna Extraction ◽

Respiratory Syndrome Virus ◽

Major Advance ◽

Rt Pcr ◽

Screening Programs ◽

Global Pandemic ◽

Gene Coding ◽

Large Scale Screening

ABSTRACTThe severe acute respiratory syndrome virus, SARS-CoV-2 (hereafter COVID-19), rapidly achieved global pandemic status, provoking large-scale screening programs in many nations. Their activation makes it imperative to identify methods that can deliver a diagnostic result at low cost. This paper describes an approach which employs sequence variation in the gene coding for its envelope protein as the basis for a scalable, inexpensive test for COVID-19. It achieves this by coupling a simple RNA extraction protocol with low-volume RT-PCR, followed by E-Gel screening and sequencing on high-throughput platforms to analyze 10,000 samples in a run. Slight modifications to the protocol could support screening programs for other known viruses and for viral discovery. Just as the $1,000 genome is transforming medicine, a $1 diagnostic test for viral and bacterial pathogens would represent a major advance for public health.

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The frequency of Tay-Sachs disease causing mutations in the Brazilian Jewish population justifies a carrier screening program

Sao Paulo Medical Journal ◽

10.1590/s1516-31802001000400007 ◽

2001 ◽

Vol 119 (4) ◽

pp. 146-149 ◽

Cited By ~ 7

Author(s):

Roberto Rozenberg ◽

Lygia da Veiga Pereira

Keyword(s):

Carrier Frequency ◽

Jewish Population ◽

Screening Program ◽

Disease Incidence ◽

Carrier Screening ◽

Restriction Enzyme Digestion ◽

Ashkenazi Jewish ◽

Screening Programs ◽

Ashkenazi Jewish Population ◽

Tay Sachs Disease

CONTEXT: Tay-Sachs disease is an autosomal recessive disease characterized by progressive neurologic degeneration, fatal in early childhood. In the Ashkenazi Jewish population the disease incidence is about 1 in every 3,500 newborns and the carrier frequency is 1 in every 29 individuals. Carrier screening programs for Tay-Sachs disease have reduced disease incidence by 90% in high-risk populations in several countries. The Brazilian Jewish population is estimated at 90,000 individuals. Currently, there is no screening program for Tay-Sachs disease in this population. OBJECTIVE: To evaluate the importance of a Tay-Sachs disease carrier screening program in the Brazilian Jewish population by determining the frequency of heterozygotes and the acceptance of the program by the community. SETTING: Laboratory of Molecular Genetics - Institute of Biosciences - Universidade de São Paulo. PARTICIPANTS: 581 senior students from selected Jewish high schools. PROCEDURE: Molecular analysis of Tay-Sachs disease causing mutations by PCR amplification of genomic DNA, followed by restriction enzyme digestion. RESULTS: Among 581 students that attended educational classes, 404 (70%) elected to be tested for Tay-Sachs disease mutations. Of these, approximately 65% were of Ashkenazi Jewish origin. Eight carriers were detected corresponding to a carrier frequency of 1 in every 33 individuals in the Ashkenazi Jewish fraction of the sample. CONCLUSION: The frequency of Tay-Sachs disease carriers among the Ashkenazi Jewish population of Brazil is similar to that of other countries where carrier screening programs have led to a significant decrease in disease incidence. Therefore, it is justifiable to implement a Tay-Sachs disease carrier screening program for the Brazilian Jewish population.

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One-step integration of amorphous RuBx and crystalline Ru nanoparticles into B/N-doped porous carbon polyhedrals for robust electrocatalytic activity towards HER in both acidic and basic media

Journal of Materials Chemistry A ◽

10.1039/d1ta08512c ◽

2022 ◽

Author(s):

Jie Tang ◽

Biao Wang ◽

Yanzheng Zhang ◽

Xiao-Hua Zhang ◽

Qinghui Shen ◽

...

Keyword(s):

Hydrogen Production ◽

Hydrogen Evolution ◽

Porous Carbon ◽

Electrocatalytic Activity ◽

Large Scale ◽

Low Cost ◽

Water Electrolysis ◽

Ru Nanoparticles ◽

One Step

As a research hot in hydrogen production by water electrolysis, exploring efficient, stable and low-cost hydrogen evolution catalysts is highly desirable and significant for the development of large-scale water electrolysis,...

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Faecal immunochemical test-based colorectal cancer screening in Mexico: an initial experience

Family Practice ◽

10.1093/fampra/cmz078 ◽

2020 ◽

Vol 37 (3) ◽

pp. 321-324 ◽

Cited By ~ 1

Author(s):

José María Remes-Troche ◽

Gabriela Hinojosa-Garza ◽

Priscilla Espinosa-Tamez ◽

Arturo Meixueiro-Daza ◽

Peter Grube-Pagola ◽

...

Keyword(s):

Colorectal Cancer ◽

Potential Benefit ◽

Large Scale ◽

Screening Program ◽

Preliminary Evidence ◽

Premalignant Lesions ◽

Middle Income ◽

Screening Programs ◽

Crc Screening ◽

Middle Income Countries

Abstract Background In middle-income countries, the burden of colorectal cancer (CRC) is increasing in parallel with resources for diagnosis and treatment. There is a potential benefit of CRC screening programs in Mexico. Objective Since there are no organized screening programs in the country, we explored the willingness of individuals to complete a faecal immunochemical testing (FIT) based CRC screening program and its potential benefit in Mexico. Methods We conducted a CRC screening program pilot in Veracruz, Mexico, during 2015–16 using FIT. Individuals with FIT results >100 ng of haemoglobin/ml buffer were referred for diagnostic colonoscopy. Results Of 473 FIT kits distributed to adults aged 50–75, 85.8% (406) were completed by participants and analysed in the laboratory. Of these, 5.9% (24/406) of test results showed >100 ng haemoglobin/ml. Twenty-one participants completed colonoscopy. The positive predictive value of FIT >100 ng haemoglobin/ml for premalignant lesions was 33%. Conclusion These results provide preliminary evidence of the willingness of individuals to complete FIT-based CRC screening program in Mexico. However, further evaluation of health systems resources will be needed prior to large-scale implementation of CRC screening programs.

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Implementation of Ultraportable Echocardiography in an Adolescent Sudden Cardiac Arrest Screening Program

Clinical Medicine Insights Cardiology ◽

10.4137/cmc.s15779 ◽

2014 ◽

Vol 8 ◽

pp. CMC.S15779 ◽

Cited By ~ 4

Author(s):

Thomas E. Vanhecke ◽

James E. Weber ◽

Matthew Ebinger ◽

Kimberly Bonzheim ◽

Frank Tilli ◽

...

Keyword(s):

Physical Examination ◽

Medical History ◽

Large Scale ◽

Screening Program ◽

Sudden Cardiac Arrest ◽

Structural Abnormality ◽

Screening Programs ◽

Structural Abnormalities ◽

Echocardiographic Examination ◽

Medical History Questionnaire

Background Over a 12-month period, adolescent heart-screening programs were performed for identifying at-risk adolescents for sudden cardiac death (SCD) in our community. Novel to our study, all adolescents received an abbreviated, ultraportable echocardiography (UPE). In this report, we describe the use of UPE in this screening program. Methods and Results Four hundred thirty-two adolescents underwent cardiac screening with medical history questionnaire, physical examination, 12-lead electrocardiogram (ECG), and an abbreviated transthoracic echocardiographic examination. There were 11 abnormalities identified with uncertain/varying clinical risk significance. In this population, 75 adolescents had a murmur or high ECG voltage, of which only three had subsequent structural abnormalities on echocardiography that may pose risk. Conversely, UPE discovered four adolescents who had a cardiovascular structural abnormality that was not signaled by the 12-lead ECG, medical history questionnaire, and/or physical examination. Conclusions The utilization of ultraportable, handheld echocardiography is feasible in large-scale adolescent cardiovascular screening programs. UPE appears to be useful for finding additional structural abnormalities and for risk-stratifying abnormalities of uncertain potential of adolescents’ sudden death.

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Unrecognized Cardiovascular Abnormalities Detected Through a Community Cardiovascular Screening Program

Journal of Diagnostic Medical Sonography ◽

10.1177/8756479320905836 ◽

2020 ◽

Vol 36 (3) ◽

pp. 234-242

Author(s):

S. Michelle Bierig ◽

Anita Arnold ◽

Lynne C. Einbinder ◽

Eric Armbrecht ◽

Thomas Burroughs

Keyword(s):

Large Scale ◽

Screening Program ◽

Ankle Brachial Index ◽

Positive Test ◽

Screening Tests ◽

Early Detection Of Disease ◽

Screening Programs ◽

Cardiovascular Screening ◽

Subclinical Disease ◽

Screening Protocol

Objective: Self-referral community cardiovascular screening programs (CCSPs) have a potential to reduce outcome events through early detection of disease. This study evaluated the characteristics of a population that could predict a positive test. Materials and Methods: Participants who completed a cardiovascular screening protocol were compared. The screening protocol included a blood pressure (BP), Doppler ankle brachial index (ABI) testing, a limited carotid sonogram, a limited aortic sonogram, electrocardiogram (ECG), and limited transthoracic echocardiogram (TTE). Results: Screenings were performed on 205 participants (58% female, 68 ± 9 years of age). Sixty-seven (34%) participants were abnormal in at least one of the following screening tests: ABI (2%), carotid sonogram (6%), aortic sonogram (3%), ECG (11%), and TTE (22%). Although 60.5% of the participants reported recent symptoms, there were no differences in normal or abnormal results of participants presenting with or without symptoms ( P = .06). Income was not a predictor of abnormal test results (odds ratio, 0.76; 95% confidence interval, 0.55–0.97; P = .19). Multivariate analysis demonstrated, when controlling for age greater than 75 years, that participants taking BP medication was the only variable that predicted a positive test result. Conclusion: One-third of patient results were abnormal, regardless of symptoms or lack thereof, suggestive of subclinical disease. Further large-scale studies would demonstrate the role of CCSPs in risk stratifying participants.

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Cystic Fibrosis

Archives of Pathology & Laboratory Medicine ◽

10.5858/1999-123-1041-cf ◽

1999 ◽

Vol 123 (11) ◽

pp. 1041-1046 ◽

Cited By ~ 1

Author(s):

Wayne W. Grody

Keyword(s):

Cystic Fibrosis ◽

Screening Program ◽

Molecular Genetic ◽

The United States ◽

Carrier Screening ◽

Cftr Gene ◽

Current Status ◽

Molecular Heterogeneity ◽

Screening Programs ◽

Cftr Mutations

Abstract Objective.—To review the current status of scientific knowledge and opinion regarding molecular genetic testing of mutations in the CFTR gene for purposes of diagnosis and population carrier screening of cystic fibrosis (CF). Data Sources.—Published research findings on the nature of the CFTR gene, pilot population screening studies in the United States and Europe, and ongoing deliberations of professional and governmental agencies considering implementation of widespread testing. Study Selection.—Findings relevant to the molecular heterogeneity of CFTR mutations and its implications for population carrier screening were considered. Data Extraction.—Information was extracted from studies published by us and others, as made available to recent consensus panels and professional committees. Data Synthesis.—These data were reevaluated in light of recent movements in professional and public policy regarding acceptability and desirability of widespread CF mutation testing. Effects to date of such testing on patient outcomes is reported. Conclusions.—The ability to test for CFTR mutations at the molecular level has already improved the diagnosis of symptomatic patients and expanded the reproductive options of family members of CF patients. The same technology also holds promise of identifying asymptomatic carriers and at-risk couples without family history in the general population so that they too might be offered prenatal diagnosis or other options. However, a number of key questions remain to be worked out before a widespread national screening program can be put into practice. These include the target population to be offered testing (the entire population vs high-risk ethnic groups), the size and nature of the mutation test panel (universal vs ethnic specific), the inclusion or exclusion of CFTR variants that do not cause classical CF, the optimal testing technology, appropriate standards for laboratory quality assurance, and the development of sufficient educational materials and genetic counseling resources for test delivery, reporting, and interpretation. The answers to these questions will be relevant not only to CF testing but also to many other large-scale molecular genetic screening programs being considered in the future.

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