[Congenital insensitivity to pain, anhidrosis and premature loss of baby teeth as a symptoms of rare neuropathy].
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Disease Progression↗
Biomedical subjects
Marja Hietala
Publications and source records attributed to Marja Hietala.
Ethical issues in the diagnostic genetic testing process.
The diagnostic genetic testing process has certain unique ethical features and deserves special consideration. The purpose of this study was to determine through empirical research, using focussed interview, what ethical issues are involved in the diagnostic genetic testing process. This article describes views and perceptions of adult patients, parents of child patients and various personnel groups (n=30). The ethical issues were analysed classified into three main categories: a) personnel characteristics, including personality, professional skills, morals and values; b) realization of ethical principles in the examination process, with subcategories of knowledge, autonomy, data protection and equity; and c) consequences of genetic testing, including patients' control over their own lives, manifestation of heterogeneity and outlook on the world. Problematic ethical issues in all three main categories were described in a more many-sided way by parents and personnel than by adult patients. In the future, attention should be paid to the content areas highlighted by the study, in both clinical practice and further studies.
Adult↗
Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer.
Uterine leiomyomata (fibroids) are common and clinically important tumors, but little is known about their etiology and pathogenesis. We previously mapped a gene that predisposes to multiple fibroids, cutaneous leiomyomata and renal cell carcinoma to chromosome 1q42.3-q43 (refs 4-6). Here we show, through a combination of mapping critical recombinants, identifying individuals with germline mutations and screening known and predicted transcripts, that this gene encodes fumarate hydratase, an enzyme of the tricarboxylic acid cycle. Leiomyomatosis-associated mutations are predicted to result in absent or truncated protein, or substitutions or deletions of highly conserved amino acids. Activity of fumarate hydratase is reduced in lymphoblastoid cells from individuals with leiomyomatosis. This enzyme acts as a tumor suppressor in familial leiomyomata, and its measured activity is very low or absent in tumors from individuals with leiomyomatosis. Mutations in FH also occur in the recessive condition fumarate hydratase deficiency, and some parents of people with this condition are susceptible to leiomyomata. Thus, heterozygous and homozygous or compound heterozygous mutants have very different clinical phenotypes. Our results provide clues to the pathogenesis of fibroids and emphasize the importance of mutations of housekeeping and mitochondrial proteins in the pathogenesis of common types of tumor.
Alleles↗
Evidence of a founder effect for the RETGC1 (GUCY2D) 2943DelG mutation in Leber congenital amaurosis pedigrees of Finnish origin.
Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies. It is a genetically heterogeneous condition as six disease-causing genes have been hitherto identified. Among them, RETGC1 (GUCY2D), is more frequently implicated in our series of LCA patients. Interestingly, 70 % of the families with RETGC1 mutations are originating from Mediterranean countries, the remaining families (30%) being originating from various countries across the world. Here, we report, the identification of the same homozygous RETGC1 nonsense mutation in three unrelated and non-consanguineous LCA families of Finnish origin, suggesting a founder effect. Interestingly, no linkage desequilibrium was found using polymorphic markers flanking the RETGC1 gene, supporting the view that the mutation is very ancient. Haplotype studies and Bayesian calculation point the founder mutation to 150 generations (95% credible interval 80-240 generations), i.e., 3000 years ago.
Blindness↗