KIF1Cmutations in two families with hereditary spastic paraparesis and cerebellar dysfunction
| العنوان: | KIF1Cmutations in two families with hereditary spastic paraparesis and cerebellar dysfunction |
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| المؤلفون: | Ali Benomar, Giovanni Stevanin, Alexis Brice, Marion Gaussen, Alexandra Durr, Simon Edvardson, Markus Schuelke, Talya Dor, Ahmed Bouhouche, Naima Bouslam, Yuval Cinnamon, Avraham Shaag, Laure Raymond, Vincent Meyer |
| المصدر: | Journal of Medical Genetics. 51:137-142 |
| بيانات النشر: | BMJ, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Adolescent, Genetic Linkage, Hereditary spastic paraplegia, DNA Mutational Analysis, Molecular Sequence Data, Nonsense mutation, Kinesins, Biology, Polymorphism, Single Nucleotide, Consanguinity, Young Adult, Cerebellar Diseases, Genetic linkage, Genetics, medicine, Spastic, Humans, Missense mutation, Amino Acid Sequence, Spasticity, Child, Genetic Association Studies, Genetics (clinical), KIF1A, Base Sequence, Infant, medicine.disease, Pedigree, Chromosome 17 (human), HEK293 Cells, Child, Preschool, Paraparesis, Spastic, Female, medicine.symptom |
| الوصف: | 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. |
| تدمد: | 1468-6244 0022-2593 |
| DOI: | 10.1136/jmedgenet-2013-102012 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df525dfbaa1088160e6728ce25fc28ad https://doi.org/10.1136/jmedgenet-2013-102012 |
| رقم الانضمام: | edsair.doi.dedup.....df525dfbaa1088160e6728ce25fc28ad |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14686244 00222593 |
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| DOI: | 10.1136/jmedgenet-2013-102012 |