A novel mutation in KIF5A gene causing hereditary spastic paraplegia with axonal neuropathy.
Hereditary spastic paraplegias (HSPs) include a group of neurodegenerative diseases, and so far 46 SPG loci have been mapped and 17 genes isolated. Among the autosomal dominant HSPs (AD-HSPs), SPG10 is a rare form due to mutations in KIF5A gene (locus 12q13.3). We describe the clinical, neurophysiological, morphological and genetic study of an Italian family with AD-HSP. The proband presented with an adult onset spastic paraparesis and diffuse paresthesias where neurophysiological and nerve biopsy morphological studies revealed an axonal neuropathy. Molecular genetic analysis identified a new missense mutation (c.608C>G) of KIF5A gene resulting in a serine to cysteine substitution, S203C, located in a highly conserved domain of the protein. This pedigree confirms the occurrence of an axonal peripheral neuropathy in SPG10.
Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Messina, Italy. omusumeci@unime.it
Olimpia
O
Musumeci
Maria Teresa
MT
Bassi
Anna
A
Mazzeo
Marina
M
Grandis
Claudia
C
Crimella
Andrea
A
Martinuzzi
Antonio
A
Toscano
D000251:Adenosine Triphosphatases / Q000235:genetics; D000595:Amino Acid Sequence; D001369:Axons / Q000473:pathology*; D001706:Biopsy; D055724:Electrophysiological Phenomena; D005190:Family; D019204:GTP-Binding Proteins / Q000235:genetics; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000235:genetics; D006801:Humans; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D008967:Molecular Biology; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology*; D009460:Neurologic Examination; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology*; D000074181:Spastin; D013497:Sural Nerve / Q000473:pathology
C500506:KIF5A protein, human; D008565:Membrane Proteins; C440006:ATL1 protein, human; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; D000074181:Spastin; D016547:Kinesins; C400283:SPAST protein, human