دورية أكاديمية
Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.
| العنوان: | Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects. |
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| المؤلفون: | Nikopoulos, K., Farinelli, P., Giangreco, B., Tsika, C., Royer-Bertrand, B., Mbefo, M.K., Bedoni, N., Kjellström, U., El Zaoui, I., Di Gioia, S.A., Balzano, S., Cisarova, K., Messina, A., Decembrini, S., Plainis, S., Blazaki, S.V., Khan, M.I., Micheal, S., Boldt, K., Ueffing, M., Moulin, A.P., Cremers, F.P., Roepman, R., Arsenijevic, Y., Tsilimbaris, M.K., Andréasson, S., Rivolta, C. |
| المصدر: | American journal of human genetics, vol. 99, no. 3, pp. 770-776 |
| سنة النشر: | 2016 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Aged, Alleles, Animals, Cadaver, Cell Cycle Proteins/genetics, Cell Cycle Proteins/metabolism, Cilia/pathology, Cohort Studies, Cone-Rod Dystrophies/complications, Cone-Rod Dystrophies/genetics, Cone-Rod Dystrophies/pathology, Cone-Rod Dystrophies/physiopathology, Exome/genetics, Eye/embryology, Eye/metabolism, Eye Proteins/metabolism, Female, Fibroblasts/pathology, Greece, Hearing Loss, Sensorineural/complications, Sensorineural/genetics, Sensorineural/pathology, Sensorineural/physiopathology, Heterozygote, Homozygote, Humans, Introns/genetics, Male, Mice |
| الوصف: | Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0002-9297 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/27588451; info:eu-repo/semantics/altIdentifier/eissn/1537-6605; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_4A7C86DC11B43; https://serval.unil.ch/notice/serval:BIB_4A7C86DC11B4Test; urn:issn:0002-9297; https://serval.unil.ch/resource/serval:BIB_4A7C86DC11B4.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_4A7C86DC11B43Test |
| DOI: | 10.1016/j.ajhg.2016.07.009 |
| الإتاحة: | https://doi.org/10.1016/j.ajhg.2016.07.009Test https://serval.unil.ch/notice/serval:BIB_4A7C86DC11B4Test https://serval.unil.ch/resource/serval:BIB_4A7C86DC11B4.P001/REF.pdfTest http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_4A7C86DC11B43Test |
| حقوق: | info:eu-repo/semantics/openAccess ; Copying allowed only for non-profit organizations ; https://serval.unil.ch/disclaimerTest |
| رقم الانضمام: | edsbas.749CC6F7 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00029297 |
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| DOI: | 10.1016/j.ajhg.2016.07.009 |