Preconception cystic fibrosis carrier screening: costs and consequences.

The objective of the study was to determine net costs of four potential preconception cystic fibrosis (CF) carrier screening strategies, and to identify the most important cost-related parameters. An estimate was made of the costs of screening carried out during general practitioner (GP) consultations, and screening carried out during group educational sessions. Two test strategies were evaluated: single-entry two-step (SETS) and double- entry two-step (DETS). Several sensitivity analyses were performed. Under the baseline assumptions, SETS screening during GP consultations was the least expensive (net costs US dollar 1,111,354 per year). The sensitivity analysis showed that the costs depend greatly on the estimated lifetime costs of care for a CF patient and the strategy used to inform the target population. Adaptations could be made to the screening program, resulting in economic savings while the primary goal of the screening--to enable participants to make an autonomous informed choice--is guaranteed.

Preconceptional cystic fibrosis carrier screening: attitudes and intentions of the target population.

The aim of this study was to assess the attitudes and intentions of individuals planning a pregnancy with regard to preconceptional cystic fibrosis (CF) carrier screening and to determine factors associated with a positive and negative/neutral intention to have the test. A survey, based on a questionnaire, was conducted among a stratified random sample of 303 recently married couples (606 individuals). Of the eligible individuals, 70% (n = 380) participated. Of the respondents, 73% had a positive attitude toward a routine offer of preconceptional CF carrier screening, and 56% had the intention to participate in a screening program. A positive intention to have the test was associated with high perceived anticipation of regret, intended preconceptional behavior, high perceived pressure from experts, high perceived consequences of the test results, low perceived barriers, and low perceived negative consequences for family members. These results suggest that the offer of routine preconceptional CF carrier screening would lead to substantial acceptance among couples planning a pregnancy. Several variables related with intention were identified.

New KIT mutations in patients with piebaldism.

BACKGROUND: Piebaldism is an autosomal dominantly inherited disorder characterized by congenital leukoderma, typically on the forehead, abdomen, and knees. The leukoderma is usually stable throughout life. KIT mutations have been demonstrated in about 75% of patients with piebaldism. OBJECTIVES: To identify KIT mutations of the family with piebaldism and examine genotype-phenotype correlations in this disorder. METHODS: PCR-direct-sequencing technique using genomic DNA from peripheral leukocytes. RESULTS: We have studied 10 individuals within six piebaldism families and able to identify six novel mutations in the KIT gene in patients with piebaldism. These include four frameshift mutations: 142delG, 1768-1769delAG, 2139delC, 2246-2249delAAAG, and two missense mutations: M541L, Y870C. CONCLUSIONS: These six new mutations are associated with phenotypes that are well in accordance with our knowledge of genotype-phenotype correlations in KIT.

Current practice and future interest of GPs and prospective parents in pre-conception care in The Netherlands.

BACKGROUND: Evidence for the effectiveness of pre-conception care is growing. GPs are among the possible providers of pre-conception care. OBJECTIVES: Our first aim was to investigate current pre-conception care activities of GPs and to determine whether prospective parents would visit the GP in the existing health care system. A further aim was to determine the interest of GPs and prospective parents in the introduction of pre-conception care clinics. METHODS: A survey was conducted among 200 GPs and 303 recently married couples (606 individuals). RESULTS: Of the eligible GPs, 52% (n = 102) participated, as did 70% (n = 381) of the eligible individuals who are planning a pregnancy. In the current situation, only a few individuals visit their GP pre-conceptionally, and many GPs do not discuss family history or consanguinity with prospective parents. In general, the GPs and prospective parents had a positive attitude towards the introduction of pre-conception care clinics. CONCLUSION: Since most GPs and prospective parents favoured the introduction of pre-conception care, future research should focus on the most appropriate way of implementation.

Attitudes of potential providers towards preconceptional cystic fibrosis carrier screening.

To determine the attitudes of potential providers (general practitioners and Community Health Service workers) towards preconceptional cystic fibrosis (CF) carrier screening and to determine which factors are associated with a positive attitude. A survey was conducted among 200 general practitioners (GPs) and 134 Community Health Service (CHS) workers. Fifty-two percent of the eligible GPs participated and 84% of the CHS workers. Fifty-five percent of the GPs and 73% of the CHS workers had a positive attitude towards routinely offering CF carrier screening, and more than 80% were in favor of informing the target population about the possibility of having a CF carrier test. A positive attitude was associated with (a) high perceived severity of CF (b) religion (nonreligious compared to Reformed), (c) low perceived barriers, and (d) high perceived test reliability. The care providers who are most likely to be involved in a preconceptional CF carrier screening program, i.e. GPs and CHS workers, generally have a positive attitude towards the implementation of such a program.

How should preconceptional cystic fibrosis carrier screening be provided? Opinions of potential providers and the target population.

BACKGROUND: Since the identification of the cystic fibrosis (CF) gene, large-scale CF carrier screening has become possible. One possible target group is couples planning a pregnancy (preconceptional screening), providing a maximum number of reproductive options and a minimum of time constraints. OBJECTIVES: To identify obstacles in the implementation of a preconceptional CF carrier screening programme, to find out how potential providers and the target population think the screening should be implemented, and to determine whether potential providers think they are able to provide the screening programme. METHODS: A survey was conducted among 200 general practitioners (GPs), 134 Municipal Health Service (MHS) workers and 303 recently married couples. RESULTS: 52% (102/197) of the eligible GPs participated, 84% (113/134) of the MHS workers and 70% (380/544) of the individuals planning a pregnancy. In general, potential providers and the target population had a positive attitude towards CF screening. Preferred methods of informing the target population were: in leaflets, during a GP consultation for those people seeking advice before pregnancy, and sending a personal invitation to all people of reproductive age. Potential providers believed that they would be able to provide the screening programme. Important perceived obstacles were the absence of a preconceptional care setting, high workload, and lack of financial resources. CONCLUSION: Different intervention strategies will be necessary to overcome the obstacles in the implementation. The positive attitude towards CF carrier screening in combination with the willingness of the potential providers to participate in the screening programme will make it easier to overcome the obstacles.

Evaluation of cystic fibrosis carrier screening programs according to genetic screening criteria.

Genetic screening programs should meet certain criteria before they can be introduced into the community. The aim of this study was to discuss pilot studies for cystic fibrosis (CF) carrier screening before and during pregnancy in the light of important genetic screening criteria. Overall, CF carrier screening meets the prerequisites that justify screening. However, more specific criteria for the development of screening programs were not always taken into consideration. Most project leaders concentrated on uptake as an important outcome, and less on informed decision-making. To further investigate the long-term psychological and social effects of genetic screening, continuous monitoring of screening projects is recommended.

Expanding phenotype of XNP mutations: mild to moderate mental retardation.

Mutations in the XNP gene have been reported in alpha thalassemia/mental retardation (MR) syndrome (ATR-X) and other severe X-linked MR conditions with facial dysmorphisms. In this report, we describe a missense mutation in exon 18 in a family with borderline to moderate MR. Like other disorders associated with an XNP mutation, skewed X-inactivation was found in all carrier females in this family. Only retrospective examination revealed childhood facial hypotonia and HbH inclusions in some of the affected males. These results expand the spectrum of clinical phenotypes known to be due to mutations in the XNP gene, and indicate that XNP mutation analysis should not be restricted to patients with severe MR and characteristic facial features.