Phenotypic analysis of autosomal dominant hereditary spastic paraplegia linked to chromosome 8q.
OBJECTIVE
To describe clinical, electrophysiologic, neuroimaging, and muscle biopsy features in a hereditary spastic paraplegia (HSP) kindred linked to a new HSP locus on chromosome 8q.


BACKGROUND
HSP is a genetically diverse group of disorders characterized by insidiously progressive spastic weakness in the legs. We recently analyzed a Caucasian kindred with autosomal dominant HSP and identified tight linkage to a novel HSP locus on chromosome 8q23-24.


METHODS
Clinical analysis, nerve conduction studies, electromyography, somatosensory evoked potentials, MRI of brain and spinal cord, and muscle biopsy for mitochondrial analysis were performed in members of the first HSP kindred linked to chromosome 8q.


RESULTS
Fifteen individuals showed insidiously progressive spastic paraparesis beginning between ages 22 and 60 years (average, 37.2 years). Spinal cord MRI in 1 moderately affected subject showed significant atrophy of the thoracic spinal cord as determined by cross-sectional area measurements. Somatosensory evoked potential recording, electromyography, nerve conduction studies, and muscle biopsy, including histochemical and biochemical analysis of mitochondrial function, were normal.


CONCLUSIONS
The phenotype in this family is that of typical, but severe, uncomplicated HSP. Other than apparently increased severity, there were no clinical features that distinguished this family from autosomal dominant HSP linked to loci on chromosomes 2p, 14q, and 15q. This clinical similarity between different genetic types of autosomal dominant HSP raises the possibility that genes responsible for these clinically indistinguishable disorders may participate in a common biochemical cascade. Normal results of muscle histochemical and biochemical analysis suggest that mitochondrial disturbance, a feature of chromosome 16-linked autosomal recessive HSP due to paraplegin gene mutations, is not a feature of chromosome 8q-linked autosomal dominant HSP and may not be a common factor of HSP in general.
Hedera
P
P
Department of Neurology, University of Michigan, Ann Arbor, USA.
DiMauro
S
S
Bonilla
E
E
Wald
J
J
Eldevik
O P
OP
Fink
J K
JK
D000328:Adult; D017668:Age of Onset; D001921:Brain / Q000473:pathology; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D002884:Chromosomes, Human, Pair 15; D002889:Chromosomes, Human, Pair 2; D002898:Chromosomes, Human, Pair 8; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D005684:Gait; D005799:Genes, Dominant; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology; D009431:Neural Conduction; D009460:Neurologic Examination; D010375:Pedigree; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology; D018454:Spouses
D004272:DNA, Mitochondrial