scholarly journals HBB mutations and HbA2 level: Escaping the carrier screening programs

2020 ◽  
Author(s):  
Ameneh Sharifi ◽  
Nejat Mahdieh
Keyword(s):  
Carrier Screening ◽  
Screening Programs

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

2001 ◽  
Vol 119 (4) ◽  
pp. 146-149 ◽  
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.

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

1996 ◽  
Vol 42 (9) ◽  
pp. 1398-1404 ◽  
Author(s):  
M Hietala ◽  
P Aula ◽  
A C Syvänen ◽  
A Isoniemi ◽  
L Peltonen ◽  
...  
Keyword(s):  
Primary Healthcare ◽  
Large Scale ◽  
Solid Phase ◽  
Screening Program ◽  
Low Cost ◽  
Carrier Screening ◽  
Screening Programs ◽  
One Step ◽  
Laboratory Technology ◽  
Maternity Health

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.

Cystic Fibrosis

1999 ◽  
Vol 123 (11) ◽  
pp. 1041-1046 ◽  
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.

scholarly journals Genetic landscape of recessive diseases in the Vietnamese population from large-scale clinical exome sequencing

2020 ◽  
Author(s):  
Ngoc Hieu Tran ◽  
Thanh-Huong Nguyen Thi ◽  
Hung-Sang Tang ◽  
Le-Phuc Hoang ◽  
Trung-Hieu Le Nguyen ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Cost Effective ◽  
Carrier Screening ◽  
Beta Thalassemia ◽  
Genetic Studies ◽  
Screening Programs ◽  
Pathogenic Variants ◽  
Clinical Exome Sequencing ◽  
Vietnamese Population ◽  
Effective Carrier

AbstractPurposeAccurate profiling of population-specific recessive diseases is essential for the design of cost-effective carrier screening programs. However, minority populations and ethnic groups, including Vietnamese, are still under-represented in existing genetic studies. Here we reported the first comprehensive study of recessive diseases in the Vietnamese population.MethodsClinical exome sequencing (CES) data of 4,503 disease-associated genes obtained from a cohort of 985 Vietnamese individuals was analyzed to identify pathogenic variants, associated diseases and their carrier frequencies in the population.ResultsEighty-five recessive diseases were identified in the Vietnamese population, among which seventeen diseases had carrier frequencies of at least 1% (1 in 100 individuals). Three diseases were especially prevalent in the Vietnamese population with carrier frequencies of 2-12 times higher than in other East Asia or the world populations, including Beta-thalassemia (1 in 25), citrin deficiency (1 in 33) and phenylketonuria (1 in 40). Seven novel pathogenic and three likely pathogenic variants associated with nine recessive diseases were also discovered.ConclusionsThe comprehensive profile of recessive diseases identified in this study shall enable the design of cost-effective carrier screening programs specific to the Vietnamese population. The newly discovered pathogenic variants may also exist in other populations at extremely low frequencies, thus representing a valuable resource for future research. Our study has demonstrated the advantage of population-specific genetic studies to advance the knowledge and practice of medical genetics.

scholarly journals Genetic Carrier Screening for Cystic Fibrosis, Fragile X Syndrome, Hemoglobinopathies, and Spinal Muscular Atrophy

2021 ◽  
Vol 1 (6) ◽  
Author(s):  
Elijah Herington ◽  
Jennifer Horton
Keyword(s):  
Health Care ◽  
Decision Making ◽  
Health Care Providers ◽  
Carrier Screening ◽  
Carrier Status ◽  
Care Providers ◽  
Screening Programs ◽  
Descriptive Information ◽  
Interim Period ◽  
Positive Carrier

People generally describe wanting access to carrier screening because knowing about the risk of passing along a genetic condition is considered important and supportive of their desires to be prepared. In the context of expanded carrier screening programs, this could mean that an increased number of people would want to access these programs. Supporting people who are considering carrier screening can be challenging and is likely to be more involved than simply sharing high-level descriptive information about testing details and potential outcomes. Descriptive information is important to help people understand the screening process and the types of results that could emerge from testing; however, programs might be more supportive of informed decision-making if the providers take a proactive role and are open to facilitating speculative conversations about potential ramifications in people’s actual lives. This is challenging given the expressed desire by health care providers, clinical geneticists in particular, to provide “neutral information” that patients would not experience as prescriptive. Given the challenge of supporting people making decisions about whether or not to pursue carrier screening, and the likely increase in people who would consider carrier screening if targeted programs were expanded to population-level screening, it is important to ensure that health care providers are both aware of jurisdictional carrier screening programs and competent in what carrier screening can offer their patients in terms of clinical actionability. Although this is particularly true for general practitioners who are often the primary point of contact with the health care system for their patients, it is also important for people who work in family planning clinics and women’s health clinics. Having the option to engage with carrier screening at the preconception stage was universally preferred by participants across the included studies. Compared with prenatal carrier screening, preconception carrier screening was seen as providing prospective parents with more reproductive options. Health care providers were concerned that offering carrier screening during pregnancy might lead pregnant people and their partners to confuse it with other prenatal testing which would limit people’s ability to be truly informed before deciding whether or not to pursue screening. However, if offered as a prenatal option, most people consider it important to do so as early as possible because it could be paired with other prenatal tests. Although not referred to specifically by any of the included studies, we note that offering carrier screening prenatally rather than at preconception, could place the responsibility to make the decision on cisgender women and non-binary or transgender people with uteruses. Sequentially designed carrier screening programs were the most common across the included studies; however, people moving through programs with this design found the interim period between receiving their positive carrier results and receiving their partners’ results difficult. This was particularly true for people who were already pregnant because this interim period forced them to reimagine both their relationship with the fetus and the future they had imagined with that child. Of course, this reimagining might be necessary if both partners’ screening results came back positive for the condition in question, but to stagger the return of the results could put undue anxiety on potential parents. Carrier screening will not affect everyone in the same way, and reproductive decision-making will still be complex and difficult. As such, the opportunity to engage with genetic counsellors on reproductive options following positive carrier status result is considered valuable.

Automated Assay of Hexosaminidases in Serum

1973 ◽  
Vol 19 (12) ◽  
pp. 1345-1349 ◽  
Author(s):  
J A Lowden ◽  
M A Skomorowski ◽  
F Henderson ◽  
M Kaback
Keyword(s):  
Normal Activity ◽  
Carrier Screening ◽  
Screening Programs ◽  
Automated Assay ◽  
Heat Labile ◽  
Tay Sachs Disease

Abstract In serum there are two classes of hexosaminidase. One of these is heat-labile and is inactive in children with Tay—Sachs disease. Serum from heterozygotes for Tay—Sachs disease has half the normal activity of the heat-labile enzyme. The heat-labile enzyme can be inactivated by heating serum diluted in buffer for 5 min at 60 °C. We have used this property to develop a reliable, fully automated assay for serum hexosaminidases, which can be used for mass carrier screening programs.

Current Practice and Attitudes of Australian Obstetricians Toward Population-Based Carrier Screening for Inherited Conditions

2013 ◽  
Vol 16 (2) ◽  
pp. 601-607 ◽  
Author(s):  
Zornitza Stark ◽  
John Massie ◽  
Belinda McClaren ◽  
Liane Ioannou ◽  
Nicole Cousens ◽  
...  
Keyword(s):  
Current Practice ◽  
Muscular Atrophy ◽  
Fragile X ◽  
Population Based ◽  
Carrier Screening ◽  
Successful Implementation ◽  
Online Questionnaire ◽  
Screening Programs ◽  
Pregnancy Care ◽  
E Mail

An anonymous survey of Australian Fellows of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists was conducted with the aim of understanding current practice and attitudes toward population-based carrier screening for inherited conditions in the setting of routine pregnancy care. Of 1,121 Fellows invited to complete the online questionnaire by e-mail, 237 (21%) responded, and of these 156 were practicing obstetricians and completed the whole survey. Of the respondents, 83% expressed support for population-based carrier screening for at least some conditions, with 97% supporting carrier screening for β-thalassaemia, and 83% supporting carrier screening for cystic fibrosis (CF). A small proportion of obstetricians reported offering carrier screening as part of routine pregnancy care (20% for β-thalassaemia, 8% for CF, 5% for fragile X syndrome, and 2% for spinal muscular atrophy). The main practical barriers identified for screening were cost, time constraints, and availability of supporting services. Addressing these issues is crucial for the successful implementation of population-based carrier screening programs in Australia and internationally.

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