Hemophilia B is a quasi-quantitative condition with certain mutations showing phenotypic plasticity.

Hemophilia B has been considered as a classical monogenic disorder with complete penetrance. Here, we observed that its allelic spectrum encompasses mutations that show least phenotypic variation as well as those showing phenotypic plasticity, thereby establishing hemophilia B as a quasi-quantitative condition with variable expressivity. Thus, we relocate it from simple monogenic diseases with complete penetrance into a space that marks the conceptual continuum of Mendelian to complex diseases. By computational analysis, we show that mutations showing phenotypic variation were characterized by relatively less conserved mutant sites and more tolerated conservative substitutions. We also demonstrate that consideration of continuous phenotypes renders quantitative rigor for interrogation and hence higher predictive value while analyzing for differential properties than classifications based on clinical end points. Certain mutations have been consistently reported to cause mild phenotype, calling for a check in indiscriminate termination of fetuses following prenatal diagnosis.

One principle and three fallacies of disability studies.

A question between John Harris and I is the degree to which lessons may be learned, and insights gained, from a life distinguished by physical differences. He argues it as the "aborting Beethoven fallacy", I insist on the evidence that what we learn from physical differences may be critical and life enhancing.

Is current practice around late termination of pregnancy eugenic and discriminatory? Maternal interests and abortion.

The attitudes of Australian practitioners working in clinical genetics and obstetrical ultrasound were surveyed on whether termination of pregnancy (TOP) should be available for conditions ranging from mild to severe fetal abnormality and for non-medical reasons. These were compared for terminations at 13 weeks and 24 weeks. It was found that some practitioners would not facilitate TOP at 24 weeks even for lethal or major abnormalities, fewer practitioners support TOP at 24 weeks compared with 13 weeks for any condition, and the difference in attitudes to TOP between 13 weeks and 24 weeks is most marked for pregnancies which are normal or involve a mild disorder. It is argued that a fetal abnormality criterion for late TOP is inconsistently applied, discriminatory and eugenic. Four possible moral justifications for current practice are examined, each of which would require significant changes to current practice. I argue in favour of a maternal interests criterion for any TOP.

Normas bioéticas de UNESCO para evitar prácticas eugenésicas en investigaciones biomédicas / Bioethical standards of UNESCO to avoid eugenical practices in biomedical research

The author, member of the UNESCO Bioethics Committee, participated in the preparation of the Universal Declaration about Human Genoma and Human Rights, in 1997. The aim of this work is to analyze the initial articles of such Declaration, defining the bioethical principles that defend human dignity, freedom and rights, against the madness of the present biotechnological revolution. The development of genetics for the benefit of mankind will be guaranteed if these principles are honored. Genetic discrimination, reductionism and determinism, are identified by the author as perversions that, if used by biotechnologists, can lead to the rebirth of eugenism and racism, that were condemned by the Code of Nuremberg, in 1947. Investigators must assume their responsibility, respecting the principles of human dignity, the real freedom of research and solidarity among people. This attitude will avoid the use of genetics for purposes other than the welfare of mankind

Prenatal diagnosis and selective abortion: a challenge to practice and policy.

Professionals should reexamine negative assumptions about the quality of life with prenatally detectable impairments and should reform clinical practice and public policy to improve informed decision making and genuine reproductive choice. Current data on children and families affected by disabilities indicate that disability does not preclude a satisfying life. Many problems attributed to the existence of a disability actually stem from inadequate social arrangements that public health professionals should work to change. This article assumes a pro-choice perspective but suggests that unreflective uses of prenatal testing could diminish, rather than expand, women's choices. This critique challenges the view of disability that lies behind the social endorsement of such testing and the conviction that women will or should end their pregnancies if they discover that the fetus has a disabling trait.

Lethal autonomy: the malfunction of the informed consent mechanism within the context of prenatal diagnosis of genetic variants.

In this article, Cara Dunne and Catherine Warren challenge the current role of genetic counselors in advising expectant mothers about potential genetic defects of their fetuses. They show that genetic counselors sometimes provide one-sided negative information to women undergoing prenatal diagnosis of genetic variants. This biased information promotes abortion of what are considered "defective" fetuses. The misleading information provided by the genetic counselors and the termination of the pregnancies is akin to the eugenics movement. The authors describe the early 20th century eugenics movement, explore the origin and development of the Human Genome Project, analyze the current role of genetic counseling, and explain the importance of the informed consent process to the exercise of autonomy. Dunne and Warren conclude by offering methods by which to restructure the informed consent mechanism to offer a more balanced assessment of the risks and benefits associated with genetic disability.