Retained human tissues: a molecular genetics goldmine or modern grave robbing? A legal approach to obtaining and using stored human samples.

The widespread retention of thousands of children's organs in the UK without parental consent has met with public outrage and calls for government intervention. These issues are brought to the fore by developments in molecular genetics that allow a person's full DNA sequence to be obtained from miniscule samples. The molecular genetic testing of retained organs and human tissue can greatly benefit family members and future research, but only if proposals to alter regulation can be successfully implemented. A review of present UK regulation indicates that it is both unclear and inadequate to ensure sufficient ethical/legal safeguards to satisfy public expectations. This paper reviews the legal and ethical status of previously retained samples. It discusses whether they may be regarded as abandoned if the patient cannot be traced and then used anonymously in ethically approved research. The legal status of retained samples is discussed as regards ownership and commerciality. This raises the question of who is the next of kin to give consent if the samples are to be regarded as gifted. Present proposals risk damaging the future by too much sensitivity. Getting the balance of interests right at this juncture is vital groundwork for such beneficial medical developments.

EEC (Ectrodactyly, Ectodermal dysplasia, Clefting) syndrome: heterozygous mutation in the p63 gene (R279H) and DNA-based prenatal diagnosis.

BACKGROUND: Germline mis-sense mutations in the DNA-binding domain of the p63 gene have recently been established as the molecular basis for the autosomal dominant EEC (Ectrodactyly, Ectodermal dysplasia, Clefting) syndrome. OBJECTIVES: To examine genomic DNA from a 36-year-old woman, her 58-year-old father and her 11-year-old son, all with the EEC syndrome, to determine the inherent p63 mutation and, after genetic counselling, to use knowledge of the mutation to undertake a first-trimester DNA-based prenatal diagnosis in a subsequent pregnancy. METHODS: Fetal DNA was extracted from chorionic villi and used to amplify exon 7 of p63 containing the potential mutation. Direct sequencing and restriction endonuclease digestion (loss of AciI site on mutant allele) were used for DNA-based prenatal diagnosis. RESULTS: We identified a heterozygous arginine to histidine p63 mutation, R279H, in all three affected individuals. Prenatal diagnosis demonstrated a homozygous wild-type sequence predicting an unaffected child: a healthy boy was subsequently born at full-term. CONCLUSIONS: These data expand the p63 gene mutation database and provide the first example of a DNA-based prenatal test in this ectodermal dysplasia syndrome.

Predictive genetic testing in maturity-onset diabetes of the young (MODY).

INTRODUCTION: Maturity-onset diabetes of the young (MODY) is characterized by autosomal dominant inheritance of young-onset non-insulin-dependent diabetes. It accounts for approximately 1% of Type 2 diabetes (approximately 20 000 people in the UK). Diagnostic and predictive genetic tests are now possible for 80% of MODY families. Diagnostic tests can be helpful as the diagnosis can be confirmed and the subtype defined which has implications for treatment and prognosis. However predictive genetic testing, particularly in children, raises many scientific, ethical and practical questions. METHODS: This is a case report of a family with diabetes resulting from an hepatic nuclear factor (HNF)1alpha mutation, who request a predictive test in their 5-year-old daughter. The scientific issues arising from molecular genetic testing in MODY are discussed, along with the process of genetic counselling. The views of the family and the clinical genetics team involved are presented. RESULTS: The implications of positive and negative predictive test results and the possibility of postponing the test were among many issues discussed during genetic counselling. The family remained convinced the test was appropriate for their daughter and the clinical genetics team fully supported this decision. The family, motivated by their family history of diabetes and personal experiences of the disease, wished to reduce uncertainty about their daughter's future irrespective of the result. CONCLUSIONS: This case emphasizes that decisions on predictive testing are very personal and require appropriate counselling.

Misoprostol, a synthetic prostaglandin E1 analogue, in the treatment of duodenal ulcers. A double-blind, cimetidine-controlled trial.

The effects of two dosage levels of a synthetic prostaglandin E1 analogue, misoprostol, and cimetidine on short-term duodenal ulcer healing were compared in a double-blind, endoscopically controlled 4-week study. The 66 adult patients were randomly divided into three groups, receiving either misoprostol 200 micrograms 4 times a day, misoprostol 50 micrograms 4 times a day or cimetidine 300 mg 4 times a day. Rates of healing were comparable in the three groups, with complete healing in 62% of those patients receiving cimetidine and high-dose misoprostol. Patients whose ulcers had healed were then followed up for a further 6 months in order to assess recurrence rates. Relapse rates were significantly higher in the cimetidine-treated group (85% within 6 months) than in the misoprostol-treated groups (50% in the low-dose and 38% in the high-dose group).