Carrier screening for cystic fibrosis in a prenatal setting

Maternal prenatal cystic fibrosis (CF) screening was offered from September, 1997, to April, 1999, at the Ghent University Hospital, to couples undergoing prenatal diagnosis (amniocentesis) for reasons not related to CF. Fifteen minutes were devoted to explaining CF, CF screening, and the study protocol. The purpose was to assess the short- and long-term knowledge of CF, the attitude towards carrier screening, and carriership. A total of 314 couples entered the pilot study; 13 female CF carriers were identified. None of their partners carried an identifiable mutation. Our survey results show that information about CF and CF screening can be given effectively as part of antenatal care because most couples recalled important medical and genetic issues, valued the genetic test for CF, and seemed to cope well with the results. Risk estimates and actual numbers were more difficult to process and recall. From the small number of couples in which the woman alone was found to be a carrier, there was little or no evidence of marked distress.     

Acceptability of carrier screening for cystic fibrosis during pregnancy in a German population

A pilot project offering voluntary heterozygote screening for the F508 mutation causing cystic fibrosis (CF) to 638 pregnant women attending two antenatal clinics in the eastern part of Berlin was carried out from 1990–1993. Participation was invited using an information leaflet and inclusion in the study was conditional on written informed consent. Of those invited to participate, only one refused to be tested, on the grounds of non-acceptance of prenatal diagnosis. Eighteen pregnant women were identified as carriers of the F508 mutation. All of them and their male partners accepted counselling in which the genetics of CF, its prognosis and treatment were explained, with emphasis on the meaning of heterozygosity, the fact that carriers are healthy, and the risk of an affected fetus when only one parent is identified as a heterozygote. All partners agreed to be tested for the F508 R553X and G551D mutations and a second counselling session was carried out after this test result was available. No problems were observed during initial testing but, as in other studies, we found considerable anxiety on being given the result in all couples where the woman tested positive; this was reduced substantially by counselling and when the partner tested negative. All probands found to be carriers stated that they found screening acceptable. In contrast to the cautious statement by the German Berufsverband Medizinische Genetik and the hostile reaction from a representative of the CF self-support organisation towards community-based heterozygote screening for CF, this study shows that CF screening is generally acceptable in this German population and that it is actively taken up by most pregnant women when offered.     

The copper-7 intrauterine contraceptive device: 5-year evaluation.

Over a 5-year period a family practitioner inserted copper-7 (Cu-7 intrauterine contraceptive devices (IUDs) in 134 women. The rates of continued use after 2 years, 53.0% for the women''s first IUD and 63.9% for all their IUDs, and of accidental pregnancy, 2.4%, are comparable to those in the literature. However, in this series the rate of expulsion was 0.8%, much lower than that in the literature. Fertility did not appear to be reduced in women who planned to have pregnancies after the device was removed. A carefully scrutinized technique of insertion and conscientious follow-up make the Cu-7 IUD an acceptable form of contraception for many patients in a family practice.     

Tay-Sachs disease carrier screening: a 21-year experience

This paper presents the findings of a community-based carrier screening program for Tay-Sachs disease, initiated on the University of Wisconsin-Madison campus in 1978. The Madison Community Tay-Sachs Screening Program (MCTSSP) is a collaborative, interdisciplinary program that organizes and conducts periodic screening for Tay-Sachs disease (TSD) for the purpose of identifying Tay-Sachs carriers. We present and analyze data on carrier detection with regard to various demographics, including family history of TSD, ancestry, gender, medication exposure, and illness. Individuals participating in the MCTSSP between 1978 and 1999 were primarily of the target population, and the carrier rate was within the expected range (1/25). Despite aggressive publicity efforts and a well-established program, attendance at the screens has declined. A recent survey of Jewish undergraduate students at the University of Wisconsin-Madison showed poor recall of family screen history and carrier status and reinforced the perception that utilization of the Madison screening program has been low. Ways to increase awareness of and interest in carrier screening for TSD are explored.     

Simultaneous screening for beta-thalassemia mutations by chemical cleavage of mismatch.

We used the chemical cleavage of mismatch (CCM) method to screen the beta-globin gene simultaneously for Mediterranean beta-thalassemia mutations. The beta-globin gene was amplified in two segments encompassing the whole gene and hybridized to a corresponding labeled PCR product from a normal subject. All the known mutations tested were identified and discriminated. Three beta-thalassemic subjects with previously undiagnosed mutations were identified as carriers of two rare DNA changes. The inheritance of the mutations could be traced in family studies, showing the reliability of the method even for prenatal diagnosis. The beta-globin gene polymorphisms were also detected and the framework was determined for most alleles. Our results suggest further applicability of the CCM method as a means to screen a gene simultaneously for multiple mutations.     

Implications of gynaecological abnormalities in pre-selection criteria for cervical screening: preliminary evaluation of 3602 subjects in South India

Early detection and eradication of cervical cancer and its precursor lesions through organized mass cytological screening programmes have recently gained considerable attention in developing countries. Strategies for both cost saving and effective implementation are however required for mass cervical screening in developing countries. In an early cancer detection programme conducted in South India, we analysed cytological abnormalities in 3602 women and correlated the results with other factors, including age, gynaecological complaints, number of years of married life and parity to see if pre-selection for cytologic screening was possible. Only lower grades of dysplasia were found in asymptomatic women below the age of 40 years. In asymptomatic women, malignancy and higher grades of dysplasia were confined to women with a clinically abnormal cervix only. Univariate analysis also revealed that subjects with a parity of more than 3 and a married life of more than 20 years had a significantly higher number of cytological abnormalities. However, on a multivariate analysis the increased number of marital years was not found to be an independent variable. These results suggest that asymptomatic women below the age of 40 years with a married life of less than 20 years and parity below 3, may be excluded from screening campaigns, and that pre-selection for cytologic screening is possible by introducing a programme of clinical and speculum examination of the cervix.     

Reliable and high-throughput mutation screening for beta-thalassemia by a single-base extension/fluorescence polarization assay

beta-thalassemia is one of the most common inherited diseases with incidence varying between 3% and 10% in the high-prevalence regions of South China. The molecular defects are mostly due to single-nucleotide substitutions, minor insertions, and deletions in the beta-globin gene. Large-scale population genetic screening combined with prenatal diagnosis is necessary for the effective prevention of this disease. We present a single base extension (SBE) method based on homogenous fluorescence polarization (FP) for simultaneous detection of the eight most common causative mutations [CDs 41-42 (-TCTT), IVS-2-654 (C-->T), -28 (A-->G), CD17 (A-->T), CD 71/72 (+A), CD26 (G-->A), -29 (A-->G), and CD43 (G-->T)] in the beta-globin gene in a Chinese population. This assay has been validated by a blind experiment with 100 clinical samples previously characterized by reverse dot-blot and direct sequencing. The results demonstrate that this high-throughput method is simple, reliable, and cost effective. We expect this approach can be used in large-scale genetic screening for beta-thalassemia.     

Carrier screening for phenylketonuria: comparison of two discriminant analysis procedures

Absence of a convenient, direct enzyme assay for detecting phenylketonuria (PKU) heterozygotes has resulted in continued effort to develop an accurate and reliable procedure to discriminate the heterozygous individual from the homozygous normal. Our study compares two statistical procedures that combine the semifasting plasma phenylalanine and tyrosine concentrations with the individuals' prior probability of being a heterozygous carrier in order to discriminate carriers from noncarriers. The results of this comparison indicate that the quadratic discriminant function is superior to the linear discriminant function as a method of carrier testing both in theory and in practice. An interactive computer system is described that facilitates the clinical utilization of the quadratic discriminant function.     

Carrier screening for Gaucher disease in couples of mixed ethnicity

With the advent of mutational analysis for Gaucher disease, carrier screening has been incorporated into many Jewish genetic disease screening programs. Frequencies and mutations for Gaucher disease in non-Jewish populations are less well established and the detection rate of carriers are lower. Testing is problematic for resolving residual risk in a couple of mixed ethnicity. We report the testing choices made by 20 consecutive couples of mixed ethnicity where the Ashkenazi Jewish partner was identified to be a Gaucher disease gene carrier. Carrier studies of the non-Jewish partner were elected as follows: DNA studies alone, 5 (25%); enzymatic assay, 2 (10%); both, 6 (30%); no carrier studies, 7 (35%). Of the 7 couples not electing carrier studies, one was not in a pregnancy and 6 elected prenatal diagnosis in lieu of parental testing by enzymatic analysis of amniocytes. One couple elected parental carrier studies as well as prenatal diagnosis. All couples electing prenatal Gaucher determination had amniocentesis for other indications as well (4, advanced maternal age; 4, parental anxiety). We conclude that Gaucher screening is feasible for couples of mixed ethnicity if appropriate counseling and testing are offered.     

Genetic counseling for beta-thalassemia trait following health screening in a health maintenance organization: comparison of programmed and conventional counseling.

Providing adequate counseling of patients identified in genetic screening programs is a major responsibility and expense. Adults in a health maintenance organization, unselected for interest, were screened for beta-thalassemia trait as part of preventive health care. Counseling was provided by either a trained physician (conventional counseling) or by a videotape containing the same information followed by an opportunity to question a trained physician (programmed counseling). Immediately before and after counseling, knowledge of thalassemia, knowledge of genetics, and mood change were assessed by questionnaire. Comparable mood changes and similar learning about thalassemia and genetics occurred with both counseling methods. Thus, as judged by immediate effects on knowledge and mood, videotaped instruction can greatly reduce professional time required for genetic counseling and facilitate the incorporation of genetic screening into primary health care.     

Carrier screening for spinal muscular atrophy (SMA) in 107,611 pregnant women during the period 2005-2009: a prospective population-based cohort study

Background

Spinal muscular atrophy (SMA) is the most common neuromuscular autosomal recessive disorder. The American College of Medical Genetics has recently recommended routine carrier screening for SMA because of the high carrier frequency (1 in 25–50) as well as the severity of that genetic disease. Large studies are needed to determine the feasibility, benefits, and costs of such a program.

Methods and Findings

This is a prospective population-based cohort study of 107,611 pregnant women from 25 counties in Taiwan conducted during the period January 2005 to June 2009. A three-stage screening program was used: (1) pregnant women were tested for SMA heterozygosity; (2) if the mother was determined to be heterozygous for SMA (carrier status), the paternal partner was then tested; (3) if both partners were SMA carriers, prenatal diagnostic testing was performed. During the study period, a total of 2,262 SMA carriers with one copy of the SMN1 gene were identified among the 107,611 pregnant women that were screened. The carrier rate was approximately 1 in 48 (2.10%). The negative predictive value of DHPLC coupled with MLPA was 99.87%. The combined method could detect approximately 94% of carriers because most of the cases resulted from a common single deletion event. In addition, 2,038 spouses were determined to be SMA carriers. Among those individuals, 47 couples were determined to be at high risk for having offspring with SMA. Prenatal diagnostic testing was performed in 43 pregnant women (91.49%) and SMA was diagnosed in 12 (27.91%) fetuses. The prevalence of SMA in our population was 1 in 8,968.

Conclusion

The main benefit of SMA carrier screening is to reduce the burden associated with giving birth to an affected child. In this study, we determined the carrier frequency and genetic risk and provided carrier couples with genetic services, knowledge, and genetic counseling.     

Aeropalynological study in Rohtak city, Haryana, India: a 2-year survey

An aeropalynological survey was conducted at two different sites in Rohtak city, Haryana, at a height of 1.8 m, three times a day, for two consecutive years (July 2007–June 2009). A total of 31 pollen types were identified to the lowest taxonomical level whenever possible. The major contributor to the pollen load was Cannabis sativa (28.9 %) followed by Poaceae (20.65 %), Chenopodiaceae/Amaranthaceae (10.56 %), Parthenium hysterophorus (6.80 %), Morus alba (6.15 %), Artemisia sp. (4.03 %), Cyperus sp. (3.20 %) and Eucalyptus sp. (3.07 %). Two major pollen seasons were recognized, that is, July–October and March–April, although pollen was recorded in varying concentrations all along the year. Spatial variations were also observed, with higher pollen loads at the site surrounded by dense vegetation. The study will provide preliminary but useful data to local allergologists for effective diagnosis and treatment of respiratory allergic ailments.     

Non-mydriatic Polaroid photography in screening for diabetic retinopathy: evaluation in a clinical setting

Because of fears that Polaroid colour prints produced with a non-mydriatic fundus camera may not detect important sight threatening lesions in diabetes a study was conducted comparing retinal images obtained on Polaroid prints taken in “field” conditions with those on 35 mm transparencies and fluorescein angiograms. Almost one in five (22/127) Polaroid prints could not be assessed owing to poor quality compared with 3 (2.4%) 35 mm transparencies and 2 (1.6%) fluorescein angiograms. The pick up rate of microaneurysms, haemorrhages, and hard and soft (cotton wool spots) exudates was equivalent for Polaroid prints and 35 mm transparencies of equivalent quality. In two cases with disc new vessels, however, these were not seen on the Polaroid prints.The widespread use of Polaroid colour prints obtained with a non-mydriatic camera without the necessary operative and interpretive skills further limits the usefulness of the technique.