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פותח על ידי קלירמאש פתרונות בע"מ -
KIF1C mutations in two families with hereditary spastic paraparesis and cerebellar dysfunction
Year:
2014
Source of publication :
Journal of Medical Genetics
Authors :
צינמון, יובל
;
.
Volume :
51
Co-Authors:
Dor, T., Department of Pediatrics, Neuropediatric Unit, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
Cinnamon, Y., Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Raymond, L., Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC Univ Paris VI UMR-S975, CNRS UMR 7225
INSERM U975, Hôpital de la Pitié-Salpêtrière, Paris, France, Groupe de Neurogénétique, Ecole Pratique des Hautes Etudes, Institut du Cerveau et de la Moelle épinière, Paris, France
Shaag, A., Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Bouslam, N., Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC Univ Paris VI UMR-S975, CNRS UMR 7225
INSERM U975, Hôpital de la Pitié-Salpêtrière, Paris, France, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi, Equipe de recherche des maladies neurodégéneratives (ERMN), Rabat, Morocco
Bouhouche, A., Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi, Equipe de recherche des maladies neurodégéneratives (ERMN), Rabat, Morocco
Gaussen, M., Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC Univ Paris VI UMR-S975, CNRS UMR 7225
Meyer, V., Genoscope, Evry, France
Durr, A., Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC Univ Paris VI UMR-S975, CNRS UMR 7225
INSERM U975, Hôpital de la Pitié-Salpêtrière, Paris, France, APHP, Fédération de Génétique, Hôpital de la Pitié-Salpêtrière, Paris, France
Brice, A., Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC Univ Paris VI UMR-S975, CNRS UMR 7225
Benomar, A., Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi, Equipe de recherche des maladies neurodégéneratives (ERMN), Rabat, Morocco, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi, Centre de recherche en épidémiologie clinique et essai thérapeutique (CRECET), Rabat, Morocco
Stevanin, G., Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC Univ Paris VI UMR-S975, CNRS UMR 7225
INSERM U975, Hôpital de la Pitié-Salpêtrière, Paris, France, Groupe de Neurogénétique, Ecole Pratique des Hautes Etudes, Institut du Cerveau et de la Moelle épinière, Paris, France, APHP, Fédération de Génétique, Hôpital de la Pitié-Salpêtrière, Paris, France
Schuelke, M., Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany
Edvardson, S., Department of Pediatrics, Neuropediatric Unit, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
Facilitators :
From page:
137
To page:
142
(
Total pages:
6
)
Abstract:
Background: Hereditary spastic paraparesis (HSP) (syn. Hereditary spastic paraplegia, SPG) are a group of genetic disorders characterised by spasticity of the lower limbs due to pyramidal tract dysfunction. Nearly 60 disease loci have been identified, which include mutations in two genes (KIF5A and KIF1A) that encode motor proteins of the kinesin superfamily. Here we report a novel genetic defect in KIF1C of patients with spastic paraparesis and cerebellar dysfunction in two consanguineous families of Palestinian and Moroccan ancestry. Methods and results: We performed autozygosity mapping in a Palestinian and classic linkage analysis in a Moroccan family and found a locus on chromosome 17 that had previously been associated with spastic ataxia type 2 (SPAX2, OMIM %611302). Whole-exome sequencing revealed two homozygous mutations in KIF1C that were absent among controls: a nonsense mutation (c.2191C>T, p.Arg731*) that segregated with the disease phenotype in the Palestinian kindred resulted in the entire absence of KIF1C protein from the patient's fibroblasts, and a missense variant (c.505C>T, p. Arg169Trp) affecting a conserved amino acid of the motor domain that was found in the Moroccan kindred. Conclusions Kinesin genes encode a family of cargo/ motor proteins and are known to cause HSP if mutated. Here we identified nonsense and missense mutations in a further member of this protein family. The KIF1C mutation is associated with a HSP subtype (SPAX2/ SAX2) that combines spastic paraplegia and weakness with cerebellar dysfunction.
Note:
Related Files :
Base Sequence
Female
genetic linkage
Genetics
Infant
Male
Molecular Sequence Data
עוד תגיות
תוכן קשור
More details
DOI :
10.1136/jmedgenet-2013-102012
Article number:
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
19757
Last updated date:
02/03/2022 17:27
Creation date:
16/04/2018 23:31
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Scientific Publication
KIF1C mutations in two families with hereditary spastic paraparesis and cerebellar dysfunction
51
Dor, T., Department of Pediatrics, Neuropediatric Unit, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
Cinnamon, Y., Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Raymond, L., Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC Univ Paris VI UMR-S975, CNRS UMR 7225
INSERM U975, Hôpital de la Pitié-Salpêtrière, Paris, France, Groupe de Neurogénétique, Ecole Pratique des Hautes Etudes, Institut du Cerveau et de la Moelle épinière, Paris, France
Shaag, A., Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Bouslam, N., Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC Univ Paris VI UMR-S975, CNRS UMR 7225
INSERM U975, Hôpital de la Pitié-Salpêtrière, Paris, France, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi, Equipe de recherche des maladies neurodégéneratives (ERMN), Rabat, Morocco
Bouhouche, A., Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi, Equipe de recherche des maladies neurodégéneratives (ERMN), Rabat, Morocco
Gaussen, M., Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC Univ Paris VI UMR-S975, CNRS UMR 7225
Meyer, V., Genoscope, Evry, France
Durr, A., Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC Univ Paris VI UMR-S975, CNRS UMR 7225
INSERM U975, Hôpital de la Pitié-Salpêtrière, Paris, France, APHP, Fédération de Génétique, Hôpital de la Pitié-Salpêtrière, Paris, France
Brice, A., Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC Univ Paris VI UMR-S975, CNRS UMR 7225
Benomar, A., Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi, Equipe de recherche des maladies neurodégéneratives (ERMN), Rabat, Morocco, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V Souissi, Centre de recherche en épidémiologie clinique et essai thérapeutique (CRECET), Rabat, Morocco
Stevanin, G., Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, UPMC Univ Paris VI UMR-S975, CNRS UMR 7225
INSERM U975, Hôpital de la Pitié-Salpêtrière, Paris, France, Groupe de Neurogénétique, Ecole Pratique des Hautes Etudes, Institut du Cerveau et de la Moelle épinière, Paris, France, APHP, Fédération de Génétique, Hôpital de la Pitié-Salpêtrière, Paris, France
Schuelke, M., Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany
Edvardson, S., Department of Pediatrics, Neuropediatric Unit, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel
KIF1C mutations in two families with hereditary spastic paraparesis and cerebellar dysfunction
Background: Hereditary spastic paraparesis (HSP) (syn. Hereditary spastic paraplegia, SPG) are a group of genetic disorders characterised by spasticity of the lower limbs due to pyramidal tract dysfunction. Nearly 60 disease loci have been identified, which include mutations in two genes (KIF5A and KIF1A) that encode motor proteins of the kinesin superfamily. Here we report a novel genetic defect in KIF1C of patients with spastic paraparesis and cerebellar dysfunction in two consanguineous families of Palestinian and Moroccan ancestry. Methods and results: We performed autozygosity mapping in a Palestinian and classic linkage analysis in a Moroccan family and found a locus on chromosome 17 that had previously been associated with spastic ataxia type 2 (SPAX2, OMIM %611302). Whole-exome sequencing revealed two homozygous mutations in KIF1C that were absent among controls: a nonsense mutation (c.2191C>T, p.Arg731*) that segregated with the disease phenotype in the Palestinian kindred resulted in the entire absence of KIF1C protein from the patient's fibroblasts, and a missense variant (c.505C>T, p. Arg169Trp) affecting a conserved amino acid of the motor domain that was found in the Moroccan kindred. Conclusions Kinesin genes encode a family of cargo/ motor proteins and are known to cause HSP if mutated. Here we identified nonsense and missense mutations in a further member of this protein family. The KIF1C mutation is associated with a HSP subtype (SPAX2/ SAX2) that combines spastic paraplegia and weakness with cerebellar dysfunction.
Scientific Publication
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