Pure hereditary spastic paraparesis: an exclusion map covering more than 40% of the autosomal genome.

Pure hereditary spastic paraparesis (HSP) is an upper motor neuron syndrome clinically characterized by slowly progressive weakness and spasticity of the legs. To determine the chromosomal location of the genetic defect, a five-generational Dutch family with autosomal dominant pure HSP was subjected to linkage studies. Analysis was carried out on 48 members spanning three generations, of whom 23 individuals are definitely affected.

Genetic linkage map of facioscapulohumeral muscular dystrophy and five polymorphic loci on chromosome 4q35-qter.

A genetic map of five polymorphic markers in the area of the facioscapulohumeral muscular dystrophy (FSHD) gene on chromosome 4q35-qter has been constructed. With these five markers, a number of recombinants have been identified that allow ordering of the marker and the disease loci. The most likely locus order and the relative position of the FSHD gene supported by the recombinants is centromere-D4S171-F11-D4S187-D4S163-D4S139-FS HD-telomere.

Detection of allele-specific transcripts by the polymerase chain reaction (AST-PCR).

We have applied the polymerase chain reaction to detect differences in relative amount of allele-specific transcripts of the low density lipoprotein receptor gene in individuals with heterozygous familial hypercholesterolemia (FH). This method is based on detection of loss of heterozygosity of exon-specific restriction fragment length polymorphisms present in amplified mRNA fragments as compared to amplified genomic DNA fragments. We detected loss of allele-specific mRNA in 20% of informative FH patients.