Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase.

We report a unique mutation in the D-amino acid oxidase gene (R199W DAO) associated with classical adult onset familial amyotrophic lateral sclerosis (FALS) in a three generational FALS kindred, after candidate gene screening in a 14.52 cM region on chromosome 12q22-23 linked to disease. Neuronal cell lines expressing R199W DAO showed decreased viability and increased ubiquitinated aggregates compared with cells expressing the wild-type protein.

A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia.

Objective: To perform genetic linkage analysis in a family affected with ALS and frontotemporal dementia (FTD).

Methods: The authors performed a genome-wide linkage analysis of a four-generation, 50-member Scandinavian family in which five individuals were diagnosed with ALS and nine with FTD. Linkage calculations assuming autosomal dominant inheritance of a single neurodegenerative disease manifesting as either ALS or FTD with age-dependent penetrance were performed.

A Christian approach to bioethics.

Christian moral insight into complex medical issues depends mostly on beliefs about what it is to be human, what makes for human well-being, and how social attitudes that reinforce such human values can best be strengthened. Issues concerning sex selection are used to illustrate how such beliefs work in practice. To dismiss therapeutic selection as 'playing God' is not helpful.

A new familial amyotrophic lateral sclerosis locus on chromosome 16q12.1-16q12.2.

Familial amyotrophic lateral sclerosis (FALS) affects 5%-10% of cases of amyotrophic lateral sclerosis (ALS) and is inherited as an autosomal dominant condition with incomplete penetrance. One-fifth of these cases of FALS are associated with mutations in copper/zinc-dependent superoxide dismutase (SOD1), but the gene defect in the remaining 80% of familial cases is, as yet, unknown. We have carried out a preliminary genome screen, using a U.

Clinical characteristics of SOD1 gene mutations in UK families with ALS.

Five to ten percent of patients with ALS have a family history of the disease, inheritance is usually autosomal dominant. Mutations of the SOD1 gene were first identified in a proportion of families with ALS by Rosen et al. The SOD1 gene encodes the enzyme copper zinc superoxide dismutase.

Clustering of ALS patients in central Italy due to the occurrence of the L84F SOD1 gene mutation.

Objective: To study three new apparently unrelated Italian families with ALS and several sporadic ALS patients living in the same rural area.

Background: One Italian family with ALS carrying a superoxide dismutase 1 (SOD1) gene mutation (G41S) and no regional ALS clustering has been reported in Italy.

Methods: Genetic analysis was performed by automated and manual sequencing of the SOD1 gene in 13 family members and in 6 of 10 unrelated patients with sporadic cases of ALS living in the same area.

Clinical and functional investigation of 10 missense mutations and a novel frameshift insertion mutation of the gene for copper-zinc superoxide dismutase in UK families with amyotrophic lateral sclerosis.

Mutations of the gene SOD-1, which encodes the enzyme copper-zinc superoxide dismutase, occur in patients with a familial form of amyotrophic lateral sclerosis (ALS). We investigated 71 families with more than one individual affected by ALS for clinical features and SOD-1 mutations. Mutations were identified in 14 families, indicating the presence of SOD-1 mutations in around 20% of this population.

A novel mutation of SOD-1 (Gly 108 Val) in familial amyotrophic lateral sclerosis.

A novel mutation of the SOD-1 gene which encodes the enzyme copper-zinc superoxide dismutase was identified in a family manifesting amyotrophic lateral sclerosis (ALS) in three generations. The mutation is a heterozygote point mutation in exon 4, codon 108 (GGA to GTA), predicting the substitution of valine for glycine. The mutation creates a new restriction site for the endonuclease AccI.

The relationship of spinal muscular atrophy to motor neuron disease: investigation of SMN and NAIP gene deletions in sporadic and familial ALS.

Amyotrophic lateral sclerosis (ALS) is found in a familial form in around 5-10% of cases. Of these familial cases around 20% are associated with mutations of SOD-1. The genetic basis of the disease in the remaining familial cases, and genetic risk factors in sporadic cases, are unknown.

Difficulties in distinguishing sporadic from familial amyotrophic lateral sclerosis.

Mutations of the copper/zinc superoxide dismutase (SOD-1) gene are present in around 20% of patients with a family history of amyotrophic lateral sclerosis. The finding of these mutations in patients with sporadic amyotrophic lateral sclerosis is rare. We describe a family with amyotrophic lateral sclerosis associated with the SOD-1 mutation Asp 101 Asn.

Medical ethics--a Christian view.

All ethics has a religious dimension. This paper considers how specific Christian insights concerning death, suffering, human nature and human creatureliness can help to expose more fully the moral issues at stake in some of the dilemmas faced by doctors. It ends by acknowledging the crushing burden of decision-making which rests on many in the medical profession, and indicates the importance of religious resources in dealing with this.

The ethics of resource allocation: a case study.

The paper analyses the factors involved in a series of decisions by the Newcastle Area Health Authority concerning the future of one of its hospitals, as an illustration of the way in which choices about priorities in the health service are actually made. There is no easy way to resolve the various conflicts of interest, notably in this case the competing demands of acute and chronic medicine. Difficult decisions are made more difficult, however, by the over-rigid division of medicine into compartments, by mistrust between the medical profession and administrators, and by the inordinately long time-scale of the decision-making process.

Morgagnian cataract.

It appears that morgagnian cataract is a special form of cortico-nuclear cataract. It is assumed that the process of fibre dissolution which is encountered in cortical cataract in general is speeded up and occurs en masse in morgagnian cataract. Enzymatic degradation of membrane and crystallin fibre components could then occur to produce liquefaction of the fibres and resorption of the cortical fluid.