A targeted population carrier screening program for severe and frequent genetic diseases in Israel

Background: Early detection of diseases in newborn may help in early intervention and treatment, which may either cure the disease or improve the outcome of the patient. Dubai’s Health Authority has a newborn screening program which includes screening for metabolic and genetic conditions, for hearing and vision, and for congenital heart disease. Objectives: The objectives of this study are to assess the outcome of the newborn genetic screening program, to correlate the association between the outcome of the program and demographic variables and to find out the percentage of the number of infants who were confirmed to have the genetic disease (by confirmatory tests) out of the total infants who had positive screening test results. Methods: During the period of the study from January 2018 to December 2018, a total of 7,027 newborns were tested in Dubai Health Authority facilities by the newborn genetic screening program (known as the “Step One Screening”). Blood samples were collected by heel prick on a collection paper. All samples were transported to PerkinElmer Genomics in the USA where the tests were done. The genetic disorders identified were correlated with different variables like gender and nationality. The data were entered in an excel sheet and analyzed by using SPSS software. All infants aged 0–3 months who have done newborn genetic screening at Dubai Health Authority facilities between January and December 2018 were included. Results: The incidence of screened disorders was 1:7,027 for congenital adrenal hyperplasia, 1:1,757 for congenital hypothyroidism, 1:1,757 for inborn errors of metabolism, 1:2,342 for biotinidase deficiency, 1:1,171 for hemoglobinopathies, 1:12 for hemoglobinopathy traits, and 1:10 for different genetic mutations of G6PD deficiency. Conclusions: There is a high incidence of different genetic diseases detected by newborn screening. These results justify unifying the program in the UAE and preventive programs like premarital screening and genetic counseling.

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PHENYLKETONURIA, AND GUTHRIE INHIBITION ASSAY SCREENING PROCEDURE

PEDIATRICS ◽

10.1542/peds.32.3.344 ◽

1963 ◽

Vol 32 (3) ◽

pp. 344-346

Keyword(s):

Public Health ◽

Large Scale ◽

Human Genetics ◽

Screening Program ◽

Genetic Diseases ◽

State Department ◽

The State ◽

Detection Methods ◽

Inhibition Assay ◽

Pilot Studies

Recommendations were made in view of the following facts: (1) the need for further information on the mechanisms involved in the phenotypic expressions of phenylketonuria; (2) the present lack of adequate data on the effectiveness of the Guthrie Inhibition Assay, in terms of number of cases which may be missed, factors making for positive determinations and providing other information on which to evaluate the appropriateness of the large-scale screening program proposed; (3) the undesirability of deploying inordinate resources in the evaluation of the Guthrie Inhibition Assay to the detriment of the needs of other areas of child health including phenylketonuria; (4) the indications that a multi-faceted approach to phenylketonuria would be productive, not only in resolving the problems involving this disorder but also as a model for the investigation of and application to the treatment of other genetic diseases; (5) the possibility that the Guthrie Inhibition Assay could be a useful tool in the early detection, treatment and investigation of phenylketonuria; and (6) the fact that other state health departments are participating in the Guthrie Field Trials, indicating that the California State Department of Public Health should apply its resources to a more intensive study of PKU and detection methods. The consultants made the following recommendations, through resolution, to the California State Department of Public Health. It was resolved that: 1. The State of California not be responsible at this time for initiating or recommending that the Guthrie procedure be accomplished on a state-wide basis in all newborn nurseries (one dissent). 2. The State of California initiate and coordinate the development of pilot studies in selected hospitals and medical centers throughout the State in the investigation of phenylketonuria, utilizing the Guthrie Inhibition Assay or other tests. 3. A scientific committee be appointed immediately as an advisory committee to the State Department of Public Health to develop recommendations for carrying out the suggested investigations. 4. A registry for phenylketonuria and other diseases (as listed in the recommendations by the Subcommittee on Human Genetics) be established within the framework of the State organization.

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Evaluating sequence data quality from the Swift Accel-Amplicon CFTR Panel

Scientific Data ◽

10.1038/s41597-019-0339-4 ◽

2020 ◽

Vol 7 (1) ◽

Author(s):

Marco L. Leung ◽

Deborah J. Watson ◽

Courtney N. Vaccaro ◽

Fernanda Mafra ◽

Adam Wenocur ◽

...

Keyword(s):

Cystic Fibrosis ◽

Screening Program ◽

Sequence Data ◽

Genetic Diseases ◽

Control Sample ◽

Gc Content ◽

Carrier Status ◽

Sequencing Data ◽

High Coverage ◽

Detection Rates

AbstractCystic fibrosis (CF) is one of the most common genetic diseases worldwide with high carrier frequencies across different ethnicities. Next generation sequencing of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has proven to be an effective screening tool to determine carrier status with high detection rates. Here, we evaluate the performance of the Swift Biosciences Accel-Amplicon CFTR Capture Panel using CFTR-positive DNA samples. This assay is a one-day protocol that allows for one-tube reaction of 87 amplicons that span all coding regions, 5′ and 3′UTR, as well as four intronic regions. In this study, we provide the FASTQ, BAM, and VCF files on seven unique CFTR-positive samples and one normal control sample (14 samples processed including repeated samples). This method generated sequencing data with high coverage and near 100% on-target reads. We found that coverage depth was correlated with the GC content of each exon. This dataset is instrumental for clinical laboratories that are evaluating this technology as part of their carrier screening program.

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The impact of a national population carrier screening program on cystic fibrosis birth rate and age at diagnosis: Implications for newborn screening

Journal of Cystic Fibrosis ◽

10.1016/j.jcf.2015.08.007 ◽

2016 ◽

Vol 15 (4) ◽

pp. 460-466 ◽

Cited By ~ 18

Author(s):

Patrick Stafler ◽

Meir Mei-Zahav ◽

Michael Wilschanski ◽

Huda Mussaffi ◽

Ori Efrati ◽

...

Keyword(s):

Cystic Fibrosis ◽

Newborn Screening ◽

Birth Rate ◽

Screening Program ◽

Carrier Screening ◽

Age At Diagnosis ◽

National Population ◽

The Impact

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Ethical Aspects of Genetic Screening in Israel

Science in Context ◽

10.1017/s0269889700003112 ◽

1998 ◽

Vol 11 (3-4) ◽

pp. 419-429 ◽

Cited By ~ 11

Author(s):

Michal Sagi

Keyword(s):

World Health Organization ◽

Genetic Screening ◽

Genetic Diseases ◽

Genetic Research ◽

Carrier Screening ◽

World Health ◽

Ethical Aspects ◽

The World ◽

Health Organization

The ArgumentAdvances in genetic research make it possible to identify carriers of a growing number of genetic diseases. The World Health Organization (WHO) published several preconditions for community carrier screening. This paper aims to present some of the dilemmas about screening in Israel and the difficulties in following the WHO's helpful criteria.

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The impact of the national population carrier screening program on reducing birth rates of patients with spinal muscular atrophy

Neuromuscular Disorders ◽

10.1016/j.nmd.2017.06.554 ◽

2017 ◽

Vol 27 ◽

pp. S137

Author(s):

S. Aharoni ◽

Y. Nevo ◽

N. Orenstein ◽

L. Basel-Vanagaite ◽

H. Mussaffi ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Screening Program ◽

Muscular Atrophy ◽

Carrier Screening ◽

Birth Rates ◽

National Population ◽

The Impact

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ACOG Committee Opinion No. 442: Preconception and Prenatal Carrier Screening for Genetic Diseases in Individuals of Eastern European Jewish Descent

Obstetrics and Gynecology ◽

10.1097/aog.0b013e3181bd12f4 ◽

2009 ◽

Vol 114 (4) ◽

pp. 950 ◽

Cited By ~ 89

Keyword(s):

Genetic Diseases ◽

Carrier Screening ◽

Eastern European ◽

European Jewish ◽

Jewish Descent

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

Clinical Chemistry ◽

10.1093/clinchem/42.9.1398 ◽

1996 ◽

Vol 42 (9) ◽

pp. 1398-1404 ◽

Cited By ~ 10

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.

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The Israeli national population program of genetic carrier screening for reproductive purposes. How should it be continued?

Israel Journal of Health Policy Research ◽

10.1186/s13584-019-0345-1 ◽

2019 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Joël Zlotogora

Keyword(s):

Genetic Screening ◽

Screening Program ◽

Severe Disease ◽

Carrier Screening ◽

Specific Population ◽

Arab Population ◽

Live Births ◽

Israeli Population ◽

Population Program ◽

Genetic Carrier Screening

AbstractThe Israeli population genetic screening program for reproductive purposes, is a population-specific screening that includes all known, severe diseases and relatively frequent in a specific population (carrier frequency at or above 1:60 and/or disease frequency at or above 1 in 15,000 live births). The carrier screening program is free of charge and offers testing according to disease frequency in the different groups within the population.The extraordinary technical changes that occurred in the last decade as well as the changes in the type of marriages within the Israeli population necessitate a revision in the basis of the program.The screening should include instead of only the relatively frequent variants, all the variants that were reported among patients causing a severe disease for which the natural history is well known without regard of their frequency. The population-specific screening that determine which variants are included according to the origin of the couple should be abandoned for a general screening including either all the Jewish population or all the Israeli Arab population.

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