The Experts below are selected from a list of 978 Experts worldwide ranked by ideXlab platform
Marina Scarlato - One of the best experts on this subject based on the ideXlab platform.
-
mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal charcot marie tooth type 2
Clinical Genetics, 2012Co-Authors: Claudia Crimella, C Baschirotto, Alessia Arnoldi, Alessandra Tonelli, Erika Tenderini, G Airoldi, Andrea Martinuzzi, Antonio Trabacca, Luciana Losito, Marina ScarlatoAbstract:Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT. Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2. Spastic paraplegia type 10 (SPG10) is an autosomal dominant form of hereditary spastic paraplegia (HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy chain implicated in anterograde axonal transport. KIF5A mutations were found in both pure and complicated forms of the disease; a single KIF5A mutation was also detected in a CMT2 patient belonging to an SPG10 mutant family. To confirm the involvement of the KIF5A gene in both CMT2 and SPG10 phenotypes and to define the frequency of KIF5A mutations in an Italian HSP patient population, we performed a genetic screening of this gene in a series of 139 HSP and 36 CMT2 affected subjects. We identified five missense changes, four in five HSP patients and one in a CMT2 subject. All mutations, including the one segregating in the CMT2 patient, are localized in the kinesin motor domain except for one, falling within the stalk domain and predicted to generate protein structure destabilization. The results obtained indicate a KIF5A mutation frequency of 8.8% in the Italian HSP population and identify a region of the kinesin protein, the stalk domain, as a novel target for mutation. In addition, the mutation found in the CMT2 patient strengthens the hypothesis that CMT2 and SPG10 are the extreme phenotypes resulting from mutations in the same gene.
-
Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2
Clinical Genetics, 2011Co-Authors: Claudia Crimella, C Baschirotto, Alessia Arnoldi, Alessandra Tonelli, Erika Tenderini, G Airoldi, Andrea Martinuzzi, Antonio Trabacca, Luciana Losito, Marina ScarlatoAbstract:Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT. Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2. Spastic paraplegia type 10 (SPG10) is an autosomal dominant form of hereditary spastic paraplegia (HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy chain implicated in anterograde axonal transport. KIF5A mutations were found in both pure and complicated forms of the disease; a single KIF5A mutation was also detected in a CMT2 patient belonging to an SPG10 mutant family. To confirm the involvement of the KIF5A gene in both CMT2 and SPG10 phenotypes and to define the frequency of KIF5A mutations in an Italian HSP patient population, we performed a genetic screening of this gene in a series of 139 HSP and 36 CMT2 affected subjects. We identified five missense changes, four in five HSP patients and one in a CMT2 subject. All mutations, including the one segregating in the CMT2 patient, are localized in the kinesin motor domain except for one, falling within the stalk domain and predicted to generate protein structure destabilization. The results obtained indicate a KIF5A mutation frequency of 8.8% in the Italian HSP population and identify a region of the kinesin protein, the stalk domain, as a novel target for mutation. In addition, the mutation found in the CMT2 patient strengthens the hypothesis that CMT2 and SPG10 are the extreme phenotypes resulting from mutations in the same gene.
Antonio Trabacca - One of the best experts on this subject based on the ideXlab platform.
-
KIF5A and als2 variants in a family with hereditary spastic paraplegia and amyotrophic lateral sclerosis
Frontiers in Neurology, 2018Co-Authors: Marta Simone, Antonio Trabacca, Luciana Losito, Elena Panzeri, Andrea Citterio, Maria Teresa BassiAbstract:Missense mutations within the kinesin family member 5A gene (KIF5A) are a known cause of a dominant form of hereditary spastic paraparesis (spastic paraplegia type 10- SPG10, OMIM: 604187) and of Charcot-Marie-Tooth disease type 2 (CMT2). Mutations in ALS2, the gene coding for alsin protein, have been demonstrated to be associated with a spectrum of rare autosomal recessive disorders including infantile ascending hereditary spastic paralysis (IAHSP), juvenile primary sclerosis (JPLS) with retrograde degeneration of the upper motor neurons, and juvenile ALS with involvement of both upper and lower motor neuron involvement. In this paper we describe a family in which the proband, a 14-year-old boy started manifesting an early onset (age 14 months) pure form of HSP rapidly progressing to a juvenile form of ALS. This boy carries a heterozygous missense variant in KIF5A, inherited from the father, and a homozygous missense variant in ALS2. The father, with family history of ALS, in the last few years has been developing signs and symptoms of affection of both the upper and lower motor neuron systems, with mild bulbar motor involvement and emotional lability. The patients described in this family, confirm the continuum and partial overlap of the two clinical entities, HSP and ALS, historically viewed as distinct entities. The genetic findings in this family further substantiate the genetic bases underlying the overlap, broadening the clinical spectrum associated with KIF5A mutations.
-
mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal charcot marie tooth type 2
Clinical Genetics, 2012Co-Authors: Claudia Crimella, C Baschirotto, Alessia Arnoldi, Alessandra Tonelli, Erika Tenderini, G Airoldi, Andrea Martinuzzi, Antonio Trabacca, Luciana Losito, Marina ScarlatoAbstract:Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT. Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2. Spastic paraplegia type 10 (SPG10) is an autosomal dominant form of hereditary spastic paraplegia (HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy chain implicated in anterograde axonal transport. KIF5A mutations were found in both pure and complicated forms of the disease; a single KIF5A mutation was also detected in a CMT2 patient belonging to an SPG10 mutant family. To confirm the involvement of the KIF5A gene in both CMT2 and SPG10 phenotypes and to define the frequency of KIF5A mutations in an Italian HSP patient population, we performed a genetic screening of this gene in a series of 139 HSP and 36 CMT2 affected subjects. We identified five missense changes, four in five HSP patients and one in a CMT2 subject. All mutations, including the one segregating in the CMT2 patient, are localized in the kinesin motor domain except for one, falling within the stalk domain and predicted to generate protein structure destabilization. The results obtained indicate a KIF5A mutation frequency of 8.8% in the Italian HSP population and identify a region of the kinesin protein, the stalk domain, as a novel target for mutation. In addition, the mutation found in the CMT2 patient strengthens the hypothesis that CMT2 and SPG10 are the extreme phenotypes resulting from mutations in the same gene.
-
Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2
Clinical Genetics, 2011Co-Authors: Claudia Crimella, C Baschirotto, Alessia Arnoldi, Alessandra Tonelli, Erika Tenderini, G Airoldi, Andrea Martinuzzi, Antonio Trabacca, Luciana Losito, Marina ScarlatoAbstract:Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT. Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2. Spastic paraplegia type 10 (SPG10) is an autosomal dominant form of hereditary spastic paraplegia (HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy chain implicated in anterograde axonal transport. KIF5A mutations were found in both pure and complicated forms of the disease; a single KIF5A mutation was also detected in a CMT2 patient belonging to an SPG10 mutant family. To confirm the involvement of the KIF5A gene in both CMT2 and SPG10 phenotypes and to define the frequency of KIF5A mutations in an Italian HSP patient population, we performed a genetic screening of this gene in a series of 139 HSP and 36 CMT2 affected subjects. We identified five missense changes, four in five HSP patients and one in a CMT2 subject. All mutations, including the one segregating in the CMT2 patient, are localized in the kinesin motor domain except for one, falling within the stalk domain and predicted to generate protein structure destabilization. The results obtained indicate a KIF5A mutation frequency of 8.8% in the Italian HSP population and identify a region of the kinesin protein, the stalk domain, as a novel target for mutation. In addition, the mutation found in the CMT2 patient strengthens the hypothesis that CMT2 and SPG10 are the extreme phenotypes resulting from mutations in the same gene.
Luciana Losito - One of the best experts on this subject based on the ideXlab platform.
-
KIF5A and als2 variants in a family with hereditary spastic paraplegia and amyotrophic lateral sclerosis
Frontiers in Neurology, 2018Co-Authors: Marta Simone, Antonio Trabacca, Luciana Losito, Elena Panzeri, Andrea Citterio, Maria Teresa BassiAbstract:Missense mutations within the kinesin family member 5A gene (KIF5A) are a known cause of a dominant form of hereditary spastic paraparesis (spastic paraplegia type 10- SPG10, OMIM: 604187) and of Charcot-Marie-Tooth disease type 2 (CMT2). Mutations in ALS2, the gene coding for alsin protein, have been demonstrated to be associated with a spectrum of rare autosomal recessive disorders including infantile ascending hereditary spastic paralysis (IAHSP), juvenile primary sclerosis (JPLS) with retrograde degeneration of the upper motor neurons, and juvenile ALS with involvement of both upper and lower motor neuron involvement. In this paper we describe a family in which the proband, a 14-year-old boy started manifesting an early onset (age 14 months) pure form of HSP rapidly progressing to a juvenile form of ALS. This boy carries a heterozygous missense variant in KIF5A, inherited from the father, and a homozygous missense variant in ALS2. The father, with family history of ALS, in the last few years has been developing signs and symptoms of affection of both the upper and lower motor neuron systems, with mild bulbar motor involvement and emotional lability. The patients described in this family, confirm the continuum and partial overlap of the two clinical entities, HSP and ALS, historically viewed as distinct entities. The genetic findings in this family further substantiate the genetic bases underlying the overlap, broadening the clinical spectrum associated with KIF5A mutations.
-
mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal charcot marie tooth type 2
Clinical Genetics, 2012Co-Authors: Claudia Crimella, C Baschirotto, Alessia Arnoldi, Alessandra Tonelli, Erika Tenderini, G Airoldi, Andrea Martinuzzi, Antonio Trabacca, Luciana Losito, Marina ScarlatoAbstract:Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT. Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2. Spastic paraplegia type 10 (SPG10) is an autosomal dominant form of hereditary spastic paraplegia (HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy chain implicated in anterograde axonal transport. KIF5A mutations were found in both pure and complicated forms of the disease; a single KIF5A mutation was also detected in a CMT2 patient belonging to an SPG10 mutant family. To confirm the involvement of the KIF5A gene in both CMT2 and SPG10 phenotypes and to define the frequency of KIF5A mutations in an Italian HSP patient population, we performed a genetic screening of this gene in a series of 139 HSP and 36 CMT2 affected subjects. We identified five missense changes, four in five HSP patients and one in a CMT2 subject. All mutations, including the one segregating in the CMT2 patient, are localized in the kinesin motor domain except for one, falling within the stalk domain and predicted to generate protein structure destabilization. The results obtained indicate a KIF5A mutation frequency of 8.8% in the Italian HSP population and identify a region of the kinesin protein, the stalk domain, as a novel target for mutation. In addition, the mutation found in the CMT2 patient strengthens the hypothesis that CMT2 and SPG10 are the extreme phenotypes resulting from mutations in the same gene.
-
Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2
Clinical Genetics, 2011Co-Authors: Claudia Crimella, C Baschirotto, Alessia Arnoldi, Alessandra Tonelli, Erika Tenderini, G Airoldi, Andrea Martinuzzi, Antonio Trabacca, Luciana Losito, Marina ScarlatoAbstract:Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT. Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2. Spastic paraplegia type 10 (SPG10) is an autosomal dominant form of hereditary spastic paraplegia (HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy chain implicated in anterograde axonal transport. KIF5A mutations were found in both pure and complicated forms of the disease; a single KIF5A mutation was also detected in a CMT2 patient belonging to an SPG10 mutant family. To confirm the involvement of the KIF5A gene in both CMT2 and SPG10 phenotypes and to define the frequency of KIF5A mutations in an Italian HSP patient population, we performed a genetic screening of this gene in a series of 139 HSP and 36 CMT2 affected subjects. We identified five missense changes, four in five HSP patients and one in a CMT2 subject. All mutations, including the one segregating in the CMT2 patient, are localized in the kinesin motor domain except for one, falling within the stalk domain and predicted to generate protein structure destabilization. The results obtained indicate a KIF5A mutation frequency of 8.8% in the Italian HSP population and identify a region of the kinesin protein, the stalk domain, as a novel target for mutation. In addition, the mutation found in the CMT2 patient strengthens the hypothesis that CMT2 and SPG10 are the extreme phenotypes resulting from mutations in the same gene.
Claudia Crimella - One of the best experts on this subject based on the ideXlab platform.
-
mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal charcot marie tooth type 2
Clinical Genetics, 2012Co-Authors: Claudia Crimella, C Baschirotto, Alessia Arnoldi, Alessandra Tonelli, Erika Tenderini, G Airoldi, Andrea Martinuzzi, Antonio Trabacca, Luciana Losito, Marina ScarlatoAbstract:Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT. Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2. Spastic paraplegia type 10 (SPG10) is an autosomal dominant form of hereditary spastic paraplegia (HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy chain implicated in anterograde axonal transport. KIF5A mutations were found in both pure and complicated forms of the disease; a single KIF5A mutation was also detected in a CMT2 patient belonging to an SPG10 mutant family. To confirm the involvement of the KIF5A gene in both CMT2 and SPG10 phenotypes and to define the frequency of KIF5A mutations in an Italian HSP patient population, we performed a genetic screening of this gene in a series of 139 HSP and 36 CMT2 affected subjects. We identified five missense changes, four in five HSP patients and one in a CMT2 subject. All mutations, including the one segregating in the CMT2 patient, are localized in the kinesin motor domain except for one, falling within the stalk domain and predicted to generate protein structure destabilization. The results obtained indicate a KIF5A mutation frequency of 8.8% in the Italian HSP population and identify a region of the kinesin protein, the stalk domain, as a novel target for mutation. In addition, the mutation found in the CMT2 patient strengthens the hypothesis that CMT2 and SPG10 are the extreme phenotypes resulting from mutations in the same gene.
-
a novel mutation in KIF5A gene causing hereditary spastic paraplegia with axonal neuropathy
Neurological Sciences, 2011Co-Authors: Olimpia Musumeci, Claudia Crimella, Andrea Martinuzzi, Maria Teresa Bassi, Anna Mazzeo, Marina Grandis, Antonio ToscanoAbstract: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.
-
Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2
Clinical Genetics, 2011Co-Authors: Claudia Crimella, C Baschirotto, Alessia Arnoldi, Alessandra Tonelli, Erika Tenderini, G Airoldi, Andrea Martinuzzi, Antonio Trabacca, Luciana Losito, Marina ScarlatoAbstract:Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT. Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot–Marie–Tooth type 2. Spastic paraplegia type 10 (SPG10) is an autosomal dominant form of hereditary spastic paraplegia (HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy chain implicated in anterograde axonal transport. KIF5A mutations were found in both pure and complicated forms of the disease; a single KIF5A mutation was also detected in a CMT2 patient belonging to an SPG10 mutant family. To confirm the involvement of the KIF5A gene in both CMT2 and SPG10 phenotypes and to define the frequency of KIF5A mutations in an Italian HSP patient population, we performed a genetic screening of this gene in a series of 139 HSP and 36 CMT2 affected subjects. We identified five missense changes, four in five HSP patients and one in a CMT2 subject. All mutations, including the one segregating in the CMT2 patient, are localized in the kinesin motor domain except for one, falling within the stalk domain and predicted to generate protein structure destabilization. The results obtained indicate a KIF5A mutation frequency of 8.8% in the Italian HSP population and identify a region of the kinesin protein, the stalk domain, as a novel target for mutation. In addition, the mutation found in the CMT2 patient strengthens the hypothesis that CMT2 and SPG10 are the extreme phenotypes resulting from mutations in the same gene.
Kelly Baldwin - One of the best experts on this subject based on the ideXlab platform.
-
mutation in KIF5A c 610c t causing hereditary spastic paraplegia with axonal sensorimotor neuropathy
Case Reports in Neurology, 2018Co-Authors: Mathieu Cuchanski, Kelly BaldwinAbstract:Hereditary spastic paraplegias (HSP) are a rare heterogeneous group of inherited neurodegenerative diseases characterized by progressive lower extremity spasticity and weakness. Mutations of the kinesin family member 5A (KIF5A) gene lead to a spectrum of phenotypes ranging from spastic paraplegia type 10 to Charcot-Marie Tooth Disease type 2. We report the second known case of a mutation in the KIF5A gene at c.610C>T presenting with HSP plus an axonal sensorimotor neuropathy.
-
novel mutation in KIF5A causing hereditary spastic paraplegia with axonal sensorimotor neuropathy p2 444
Neurology, 2018Co-Authors: Mathieu Cuchanski, Kelly BaldwinAbstract:Objective: The Hereditary Spastic Paraplegias (HSP) are a rare, heterogeneous group of inherited neurodegenerative diseases characterized by progressive lower extremity spasticity and weakness. Mutations of the kinesin family member 5A (KIF5A) gene lead to a spectrum of phenotypes ranging from spastic paraplegia type 10 (SPG10) to Charcot-Marie Tooth Disease Type 2. Background: A 31 year old male presented with ten years of progressive walking difficulties, stiffness in his arms and legs, and distal paresthesias. Family history is significant for a similar presenting neurologic syndrome in his father and paternal uncle. Neurologic exam revealed normal cognition, cranial nerve examination, and cerebellar examination. Sensory exam demonstrated a length dependent loss of pin prick and vibration in the hands and feet bilaterally. Motor examination revealed asymmetric weakness in the right iliopsoas, hamstring, and anterior tibialis. Tone was significantly increased in the bilateral lower extremities with sustained clonus at the ankles and bilateral extensor plantar responses. The patient’s gait was spastic with scissoring and bilateral foot inversion. Magnetic Resonance Imaging (MRI) brain with and without contrast and MRI cervical spine without contrast were both normal. Laboratory analyses for myelopathy including HTLV-1, Vitamin B12, and Syphilis were negative. EMG/NCS demonstrated a distal symmetric axonal sensory motor neuropathy in all four extremities. Genetic testing for hereditary spastic paraplegia returned positive for a mutation in the KIF5A gene (c.610C>T), consistent with spastic paraplegia type 10. Design/Methods: N/A Results: N/A Conclusions: SPG10 is caused by a mutation in the KIF5A gene encoding neuron specific kinesin heavy chain 5A. KIF5A is expressed in all neurons, which may lead to its variety of presentations including axonal neuropathy, optic neuropathy, epilepsy, and ataxia. Although axonal neuropathy has been reported in many HSP patients, we have reported the first case of HSP10 with neuropathy attributable to a mutation at c.610C>T. Disclosure: Dr. Cuchanski has nothing to disclose. Dr. Baldwin has nothing to disclose.
