Ataxia and the role of antigliadin antibodies.

BACKGROUND: Although it is acknowledged that patients with celiac disease can develop neurological complications such as ataxia, the association of antigliadin antibodies in the etiology of sporadic ataxia and the usefulness of this testing in diagnosis of ataxia is controversial. METHODS: We investigated this association by testing for the presence of IgG and IgA antigliadin antibodies in 56 ataxic patients and 59 controls. The ataxia patients were subsequently classified into three groups: sporadic, hereditary and MSA. RESULTS: Of the total ataxic patients, 6/56 (11%) were positive for either IgG or IGA antigliadin antibodies compared to the controls of which 5/59 (8%) were positive (p = 0.68). In a subgroup analysis, 4/29 (14%) of the samples in the sporadic ataxic subgroup were positive for antigliadin antibodies (IgG or IgA) compared to control (p = 0.44). Similar negative results were found in the remaining subgroup analyses. CONCLUSIONS: These results do not support an association between antigliadin antibodies and sporadic ataxias.

Genetic heterogeneity in paroxysmal nonkinesigenic dyskinesia.

Paroxysmal nonkinesigenic dyskinesia (PNKD) is characterized by attacks of dystonia or chorea lasting minutes to hours. Recently, mutations in the myofibrillogenesis regulator 1 gene (MR-1) have been identified in 10 unrelated PNKD kindreds. The authors describe a Canadian PNKD family who does not have mutations in the MR-1 gene and links to a separate locus at 2q31. This indicates that there are at least two different genes responsible for PNKD.

Mutation analysis of the sodium/hydrogen exchanger gene (NHE5) in familial paroxysmal kinesigenic dyskinesia.

Familial Paroxysmal Kinesigenic Dyskinesia (PKD) is an autosomal dominant condition characterized by attacks of dystonia or chorea triggered by sudden movements. Recently two separate loci for PKD, Episodic Kinesigenic Dyskinesia 1 (EKD1) and Episodic Kinesigenic Dyskinesia 2 (EKD2), have been mapped to chromosome 16 but the causative genes have not been identified. The Na(+)/H(+) exchanger gene (NHE5) involved in regulating intracellular pH lies in the EKD2 region. The coding region of the NHE5 gene in familial PKD was sequenced. We did not identify any mutations in the exons, intron/exon boundaries or the 5' and 3'UTR. This excludes mutations in the coding region of the NHE5 gene as a cause for familial PKD, but does not rule out a possible role of sequence variants in introns or regulatory regions.

A second paroxysmal kinesigenic choreoathetosis locus (EKD2) mapping on 16q13-q22.1 indicates a family of genes which give rise to paroxysmal disorders on human chromosome 16.

Paroxysmal kinesigenic choreoathetosis (PKC) is a rare paroxysmal movement disorder characterized by recurrent and brief attacks of choreiform or dystonic movements triggered or exacerbated by sudden voluntary movements. Some patients with PKC also have a history of infantile afebrile convulsions. PKC can be sporadic, or familial with autosomal dominant inheritance. PKC has been mapped to the pericentromeric region of human chromosome 16 in several Japanese families and in an African-American family, to regions which overlap by 9.8 cM (centiMorgan). Both regions overlap by 3.4 cM with a region containing a gene responsible for 'infantile convulsions and paroxysmal choreoathetosis' (ICCA). We have identified a second PKC locus (EKD2) on the long arm of chromosome 16 in a large Indian family with PKC. A maximum two-point LOD score of 3.66 (recombination fraction = 0.00, penetrance = 0.80) was obtained between PKC and D16S419. Haplotype and recombinant analysis localized EKD2 to a 15.8 cM region between D16S685 and D16S503. This region does not overlap with that identified in Japanese families, or with the ICCA locus. These results exclude one locus on chromosome 16 which causes both the ICCA and PKC syndromes; this suggests that there may be a cluster of genes on human chromosome 16 which lead to paroxysmal disorders.

The molecular basis and clinical management of ataxia telangiectasia.

The unique combination of phenotypic manifestations seen in ataxia telangiectasia (AT) has intrigued neurologists, oncologists, radiation biologists and immunologists for several decades. Initially, the primary care givers of AT patients are often pediatricians but neurologists will inevitably become involved in their care. Over the last few years great strides have been made in understanding the genetic basis of this disease but useful therapeutic interventions are still not available. In this article, we review the clinical features and the current understanding of the pathophysiology of the syndrome. In addition, we address issues related to genetic counseling, prenatal diagnosis, screening and implications for AT heterozygotes.

The genetics of Parkinson's disease.

Since the first description of Parkinson's disease in 1817 there have been numerous attempts to clarify the relative contribution of hereditary and environmental factors in its aetiology. Epidemiological and case-control studies as well as the existence of families with monogenic Parkinson's disease point clearly to a genetic contribution. Insights into the genetic basis of Parkinson's disease will lead to a greater understanding of the condition at a molecular level which will in turn allow the development of new rational therapeutic option.