Abstract
SPG10 is an autosomal dominant hereditary spastic paraplegia (HSP) caused by mutations in the gene KIF5A encoding the heavy chain of kinesin, a motor protein implied in motility functions within cells. Most of the KIF5A mutations are clustered in 2 areas of motor domain of the protein, the switch regions I and II, that are necessary for microtubules interaction. The set of mutations in KIF5A described so far account for a spectrum of clinical heterogeneity ranging from pure HSP to isolated peripheral nerve involvement (Charcot-Marie-Tooth phenotype) or complicated HSP phenotypes. We here describe a patient presenting with progressive walking difficulties and burning dysesthesias, numbness, and pain at distal segments of the 4 limbs. Neurological examination revealed severe spastic gait and vibratory and proprioception sensory reduction in the lower limbs. Motor and sensory nerve conduction studies disclosed axonal damage of peripheral nerves at lower limbs. We identified the novel variant c.967C.T in the KIF5A gene resulting in the R323W change, which is located at the C-terminus of the motor domain of the KIF5A protein, just upstream the linker region but out of the switch regions. Our findings confirm that the "mixed" central-peripheral involvement is the most frequent clinical picture related to KIF5A motor domain mutations and that motor domain "in toto," even outside of the switch regions, is a hot spot for pathogenic mutations. We stress the concept that detection of a peripheral axonal neuropathy in an autosomal dominant HSP patient should be regarded as an important diagnostic tool and should guide clinicians to seek, first of all, KIF5A mutations.
| Original language | English |
|---|---|
| Pages (from-to) | 153-158 |
| Number of pages | 6 |
| Journal | Journal of Clinical Neuromuscular Disease |
| Volume | 16 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 6 2015 |
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Keywords
- axonal neuropathy
- hereditary spastic paraplegias
- HSP
- KIF5A
- SPG10
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
Cite this
A novel mutation in motor domain of KIF5A associated with an HSP/axonal neuropathy phenotype. / Rinaldi, Fabrizio; Bassi, Maria T.; Todeschini, Alice; Rota, Silvia; Arnoldi, Alessia; Padovani, Alessandro; Filosto, Massimiliano.
In: Journal of Clinical Neuromuscular Disease, Vol. 16, No. 3, 06.03.2015, p. 153-158.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A novel mutation in motor domain of KIF5A associated with an HSP/axonal neuropathy phenotype
AU - Rinaldi, Fabrizio
AU - Bassi, Maria T.
AU - Todeschini, Alice
AU - Rota, Silvia
AU - Arnoldi, Alessia
AU - Padovani, Alessandro
AU - Filosto, Massimiliano
PY - 2015/3/6
Y1 - 2015/3/6
N2 - SPG10 is an autosomal dominant hereditary spastic paraplegia (HSP) caused by mutations in the gene KIF5A encoding the heavy chain of kinesin, a motor protein implied in motility functions within cells. Most of the KIF5A mutations are clustered in 2 areas of motor domain of the protein, the switch regions I and II, that are necessary for microtubules interaction. The set of mutations in KIF5A described so far account for a spectrum of clinical heterogeneity ranging from pure HSP to isolated peripheral nerve involvement (Charcot-Marie-Tooth phenotype) or complicated HSP phenotypes. We here describe a patient presenting with progressive walking difficulties and burning dysesthesias, numbness, and pain at distal segments of the 4 limbs. Neurological examination revealed severe spastic gait and vibratory and proprioception sensory reduction in the lower limbs. Motor and sensory nerve conduction studies disclosed axonal damage of peripheral nerves at lower limbs. We identified the novel variant c.967C.T in the KIF5A gene resulting in the R323W change, which is located at the C-terminus of the motor domain of the KIF5A protein, just upstream the linker region but out of the switch regions. Our findings confirm that the "mixed" central-peripheral involvement is the most frequent clinical picture related to KIF5A motor domain mutations and that motor domain "in toto," even outside of the switch regions, is a hot spot for pathogenic mutations. We stress the concept that detection of a peripheral axonal neuropathy in an autosomal dominant HSP patient should be regarded as an important diagnostic tool and should guide clinicians to seek, first of all, KIF5A mutations.
AB - SPG10 is an autosomal dominant hereditary spastic paraplegia (HSP) caused by mutations in the gene KIF5A encoding the heavy chain of kinesin, a motor protein implied in motility functions within cells. Most of the KIF5A mutations are clustered in 2 areas of motor domain of the protein, the switch regions I and II, that are necessary for microtubules interaction. The set of mutations in KIF5A described so far account for a spectrum of clinical heterogeneity ranging from pure HSP to isolated peripheral nerve involvement (Charcot-Marie-Tooth phenotype) or complicated HSP phenotypes. We here describe a patient presenting with progressive walking difficulties and burning dysesthesias, numbness, and pain at distal segments of the 4 limbs. Neurological examination revealed severe spastic gait and vibratory and proprioception sensory reduction in the lower limbs. Motor and sensory nerve conduction studies disclosed axonal damage of peripheral nerves at lower limbs. We identified the novel variant c.967C.T in the KIF5A gene resulting in the R323W change, which is located at the C-terminus of the motor domain of the KIF5A protein, just upstream the linker region but out of the switch regions. Our findings confirm that the "mixed" central-peripheral involvement is the most frequent clinical picture related to KIF5A motor domain mutations and that motor domain "in toto," even outside of the switch regions, is a hot spot for pathogenic mutations. We stress the concept that detection of a peripheral axonal neuropathy in an autosomal dominant HSP patient should be regarded as an important diagnostic tool and should guide clinicians to seek, first of all, KIF5A mutations.
KW - axonal neuropathy
KW - hereditary spastic paraplegias
KW - HSP
KW - KIF5A
KW - SPG10
UR - http://www.scopus.com/inward/record.url?scp=84924126155&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924126155&partnerID=8YFLogxK
U2 - 10.1097/CND.0000000000000063
DO - 10.1097/CND.0000000000000063
M3 - Article
VL - 16
SP - 153
EP - 158
JO - Journal of Clinical Neuromuscular Disease
JF - Journal of Clinical Neuromuscular Disease
SN - 1522-0443
IS - 3
ER -