Refinement of the SPG15 candidate interval and phenotypic heterogeneity in three large Arab families
| العنوان: | Refinement of the SPG15 candidate interval and phenotypic heterogeneity in three large Arab families |
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| المؤلفون: | Diana Zelenika, Alexander Lossos, Ali Benomar, Zohar Argov, Stephan Klebe, Alexandra Durr, Alexis Brice, Naima Bouslam, Abdelmadjid Hamri, Meriem Tazir, N. Elleuch, D. Grid, Sylvain Hanein, Giovanni Stevanin, Delphine Bacq, Vardiella Meiner, N. Birouk, Mohamed Yahyaoui, Israela Lerer |
| المساهمون: | Department of neurology, Hopital Habib Bourguiba - Habib Bourguiba Hospital [Sfax], Department of Neurogenetics, Hôpital des Spécialités, Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANR-05-MRAR-0001,Cav3pathies,Approches physiopathologique et moléculaire de la signalisation calcique dans les caveolinopathies musculaires(2005), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| المصدر: | neurogenetics neurogenetics, Springer Verlag, 2007, 8 (4), pp.307-15. ⟨10.1007/s10048-007-0097-x⟩ neurogenetics, 2007, 8 (4), pp.307-15. ⟨10.1007/s10048-007-0097-x⟩ |
| بيانات النشر: | HAL CCSD, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Male, Exon, Consanguinity, 0302 clinical medicine, Spastic, MESH: Syndrome, Genetics (clinical), Genetics, 0303 health sciences, MESH: Spastic Paraplegia, Hereditary, Chromosome Mapping, Syndrome, Arabs, Pedigree, Phenotype, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adult, Adolescent, Hereditary spastic paraplegia, MESH: Pedigree, Locus (genetics), Biology, MESH: Phenotype, Genetic determinism, 03 medical and health sciences, Cellular and Molecular Neuroscience, Gene mapping, Genetic linkage, medicine, Humans, 030304 developmental biology, Chromosomes, Human, Pair 14, MESH: Adolescent, MESH: Consanguinity, MESH: Humans, Genetic heterogeneity, Spastic Paraplegia, Hereditary, MESH: Adult, MESH: Haplotypes, medicine.disease, MESH: Male, Haplotypes, MESH: Arabs, MESH: Chromosomes, Human, Pair 14, MESH: Microsatellite Repeats, MESH: Chromosome Mapping, MESH: Female, 030217 neurology & neurosurgery, Microsatellite Repeats |
| الوصف: | Hereditary spastic paraplegia (HSP) type 15 is an autosomal recessive (AR) form of complicated HSP mainly characterized by slowly progressive spastic paraplegia, mental retardation, intellectual deterioration, maculopathy, distal amyotrophy, and mild cerebellar signs that has been associated with the Kjellin syndrome. The locus for this form of HSP, designated SPG15, was mapped to an interval of 19 cM on chromosome 14q22-q24 in two Irish families. We performed a clinical-genetic study of this form of HSP on 147 individuals (64 of whom were affected) from 20 families with AR-HSP. A genome-wide scan was performed in three large consanguineous families of Arab origin after exclusion of linkage to several known loci for AR-HSP (SPG5, SPG7, SPG21, SPG24, SPG28, and SPG30). The 17 other AR-HSP families were tested for linkage to the SPG15 locus. Only the three large consanguineous families showed evidence of linkage to the SPG15 locus (2.4 > Z (max) > 4.3). Recombinations in these families reduced the candidate region from approximately 16 to approximately 5 Mbases. Among the approximately 50 genes assigned to this locus, two were good candidates by their functions (GPHN and SLC8A3), but their coding exons and untranslated regions (UTRs) were excluded by direct sequencing. Patients had spastic paraplegia associated with cognitive impairment, mild cerebellar signs, and axonal neuropathy, as well as a thin corpus callosum in one family. The ages at onset ranged from 10 to 19 years. Our study highlights the phenotypic heterogeneity of SPG15 in which mental retardation or cognitive deterioration, but not all other signs of Kjellin syndrome, are associated with HSP and significantly reduces the SPG15 locus. |
| اللغة: | English |
| تدمد: | 1364-6745 1364-6753 |
| DOI: | 10.1007/s10048-007-0097-x⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::baf0224f5cb7a073e32a0bab10b2fe9f https://hal.archives-ouvertes.fr/hal-00281710 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....baf0224f5cb7a073e32a0bab10b2fe9f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13646745 13646753 |
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| DOI: | 10.1007/s10048-007-0097-x⟩ |