Journal article
Novel POC1A mutation in primordial dwarfism reveals new insights for centriole biogenesis
Human molecular genetics, v 24(19), pp 5378-5387
01 Oct 2015
PMID: 26162852
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
POC1A encodes a WD repeat protein localizing to centrioles and spindle poles and is associated with short stature, onychodysplasia, facial dysmorphism and hypotrichosis (SOFT) syndrome. These main features are related to the defect in cell proliferation of chondrocytes in growth plate. In the current study, we aimed at identifying the molecular basis of two patients with primordial dwarfism (PD) in a single family through utilization of whole-exome sequencing. A novel homozygous p.T120A missense mutation was detected in POC1A in both patients, a known causative gene of SOFT syndrome, and confirmed using Sanger sequencing. To test the pathogenicity of the detected mutation, primary fibroblast cultures obtained from the patients and a control individual were used. For evaluating the global gene expression profile of cells carrying p.T120A mutation in POC1A, we performed the gene expression array and compared their expression profiles to those of control fibroblast cells. The gene expression array analysis showed that 4800 transcript probes were significantly deregulated in cells with p.T120A mutation in comparison to the control. GO term association results showed that deregulated genes are mostly involved in the extracellular matrix and cytoskeleton. Furthermore, the p.T120A missense mutation in POC1A caused the formation of abnormal mitotic spindle structure, including supernumerary centrosomes, and changes in POC1A were accompanied by alterations in another centrosome-associated WD repeat protein p80-katanin. As a result, we identified a novel mutation in POC1A of patients with PD and showed that this mutation causes the formation of multiple numbers of centrioles and multipolar spindles with abnormal chromosome arrangement.
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Details
- Title
- Novel POC1A mutation in primordial dwarfism reveals new insights for centriole biogenesis
- Creators
- Asuman Koparir - Department of Medical Genetics, Istanbul University, Cerrahpasa Medical School, Istanbul, TurkeyOmer F Karatas - Erzurum Technical UniversityBetul Yuceturk - TUBITAK BILGEMBayram Yuksel - Scientific and Technological Research Council of TurkeyAli O Bayrak - TUBITAK BILGEMOmer F Gerdan - TUBITAK BILGEMMahmut S Sagiroglu - GenomicsAlper Gezdirici - İstanbul Kanuni Sultan Süleyman Eğitim ve Araştırma HastanesiKoray Kirimtay - Istanbul Technical UniversityEce Selcuk - Istanbul Technical UniversityArzu Karabay - Istanbul Technical UniversityChad J Creighton - Dan L Duncan Comprehensive Cancer CenterAdnan Yuksel - Biruni UniversityMustafa Ozen - Baylor College of Medicine
- Publication Details
- Human molecular genetics, v 24(19), pp 5378-5387
- Publisher
- Oxford University Press
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000363018100002
- Scopus ID
- 2-s2.0-84943812978
- Other Identifier
- 991022018088604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Genetics & Heredity