[Fiessinger-Leroy-Reiter syndrome in Greenland. Clinical and epidemiological aspects]. / Le syndrome de Fiessinger-Leroy-Reiter au Groenland. Aspects cliniques et épidémiologiques.

A clinical and epidemiological study of the Fiessinger Leroy Reiter syndrome was undertaken in Inuits from four Greenland cities, because of the frequency of HLA B27 antigen and venereal diseases in this population. A mean prevalence of 0.67 p. cent was found in Inuits from the west coast, of which 27.5 p. cent are carriers of the HLA B27 antigen. In Amassalik, on Greenland's east coast, where the frequency of B27 was estimated at 6.5 p. cent, the prevalence of the syndrome is 0.32 p. cent. Immunogenetic and preliminary familial data show that HLA B27 is present in 87.5 p. cent of the patients and that 34 p. cent have a close relative with the disease. Clinical data are comparable to those reported in the literature. Evolution is marred by frequent recurrences: 85 p. cent of the patients followed for more than ten (10) years present at least one recurrence. The total frequency of ankylosing spondylarthritis is 16.7 p. cent. It increases, in retrospect, to reach 45 p. cent in 22 patients followed for more than 15 years.

Mapping of genes controlling quantitative antibody production in Biozzi mice.

An extensive search for in vivo immunomodulatory genes (Im genes) was made, using highly polymorphic DNA markers (microsatellites), in F2 hybrids between the two lines of mice selected for high (H) or low (L) Ab production (Biozzi mice). H and L mice have extreme phenotypes resulting from the accumulation, during selective breeding, of genes endowed with, respectively, upward or downward additive effects on Ab production. A total genome screening with 90 microsatellite markers (polymorphic between H and L mice) was conducted in 60 F2 hybrids sorted out for their extreme phenotypes from an immunized population of 240 individuals. A difference in parental marker frequency between these two groups (measured by a chi2 test) reveals the presence of an Im gene close to the marker. Significant chi2 scores were indeed found in two regions corresponding to the MHC and Igh loci, already identified as partly contributing to the H/L phenotypic difference. A notable finding was the demonstration that a gene(s), located on the proximal part of chromosome 6, was linked with Ab responsiveness. Other markers at distinct chromosomal regions also give increased chi2 scores, the two regions most clearly pointed out being on chromosomes 4 and 8.

Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14. The French Spinal Muscular Atrophy Investigators.

Linkage analysis in twenty-five families with acute (type I) spinal muscular atrophy (SMA) showed that the mutant gene responsible for the disorder is tightly linked to the D5S39 locus. The mutation(s) causing the intermediate (type II) and juvenile chronic (type III) forms of SMA were also mapped to DNA marker D5S39 on chromosome 5 (5q12-q14). Thus, the three forms, which have been differentiated clinically on the basis of age of onset and clinical course, are most probably due to different mutations at a single locus on chromosome 5. Prenatal diagnosis of SMA type I will now be possible.

Linkage of benign familial infantile convulsions to chromosome 16p12-q12 suggests allelism to the infantile convulsions and choreoathetosis syndrome.

The syndrome of benign familial infantile convulsions (BFIC) is an autosomal dominant epileptic disorder that is characterized by convulsions, with onset at age 3-12 mo and a favorable outcome. BFIC had been linked to chromosome 19q, whereas the infantile convulsions and choreoathetosis (ICCA) syndrome, in which BFIC is associated with paroxysmal dyskinesias, had been linked to chromosome 16p12-q12. BFIC appears to be frequently associated with paroxysmal dyskinesias, because many additional families from diverse ethnic backgrounds have similar syndromes that have been linked to the chromosome 16 ICCA region. Moreover, one large pedigree with paroxysmal kinesigenic dyskinesias only, has also been linked to the same genomic area. This raised the possibility that families with pure BFIC may be linked to chromosome 16 as well. We identified and studied seven families with BFIC inherited as an autosomal dominant trait. Genotyping was performed with markers at chromosome 19q and 16p12-q12. Although chromosome 19q could be excluded, evidence for linkage in the ICCA region was found, with a maximum two-point LOD score of 3.32 for markers D16S3131 and SPN. This result proves that human chromosome 16p12-q12 is a major genetic locus underlying both BFIC and paroxysmal dyskinesias. The unusual phenotype displayed by one homozygous patient suggests that variability of the ICCA syndrome could be sustained by genetic modifiers.