دورية أكاديمية
Expanding the phenome and variome of skeletal dysplasia.
| العنوان: | Expanding the phenome and variome of skeletal dysplasia. |
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| المؤلفون: | Maddirevula S; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Alsahli S; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Alhabeeb L; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Patel N; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Alzahrani F; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Shamseldin HE; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Anazi S; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Ewida N; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Alsaif HS; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Mohamed JY; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Alazami AM; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Ibrahim N; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Abdulwahab F; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Hashem M; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Abouelhoda M; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia., Monies D; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia., Al Tassan N; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia., Alshammari M; Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Alsagheir A; Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Seidahmed MZ; Pediatric Department, Forces Hospital, Riyadh, Saudi Arabia., Sogati S; Department of Medical Genetics, King Fahad General Hospital, Jeddah, Saudi Arabia., Aglan MS; Clinical Genetics Department, Human Genetics & Genome Research Division, Center of Excellence of Human Genetics, National Research Centre, Cairo, Egypt., Hamad MH; Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Salih MA; Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Hamed AA; Department of Pediatrics and Child Health, Faculty of Medicine, University of Khartoum, Khartoum, Sudan., Alhashmi N; Department of Pediatrics, Royal Hospital, Muscat, Oman., Nabil A; Human Genetics Department, Medical Research Institute, Alexandria University, Alexandria, Egypt., Alfadli F; Department of Pediatrics, Maternity and Children's Hospital, Medina, Saudi Arabia., Abdel-Salam GMH; Clinical Genetics Department, Human Genetics & Genome Research Division, Center of Excellence of Human Genetics, National Research Centre, Cairo, Egypt., Alkuraya H; Global Eye Care, Specialized Medical Center Hospital, Riyadh, Saudi Arabia., Peitee WO; Clinical Genetics, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia., Keng WT; Clinical Genetics, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia., Qasem A; Department of Pediatric, Prince Sultan Medical Military City, Riyadh, Saudi Arabia., Mushiba AM; Department of Pediatric Subspecialties, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia., Zaki MS; Clinical Genetics Department, Human Genetics & Genome Research Division, Center of Excellence of Human Genetics, National Research Centre, Cairo, Egypt., Fassad MR; The Human Genetics Department, Medical Research Institute, Alexandria University, Alexandria, Egypt., Alfadhel M; King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, Genetics Division, Department of Pediatrics, King Abdulaziz Medical City, MNGHA, Riyadh, Saudi Arabia., Alexander S; Department of Paediatric Endocrinology and Diabetes, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK., Sabr Y; Department of Obstetrics and Gynecology, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Temtamy S; Clinical Genetics Department, Human Genetics & Genome Research Division, Center of Excellence of Human Genetics, National Research Centre, Cairo, Egypt., Ekbote AV; Clinical Genetics Unit, Christian Medical College, Vellore, India., Ismail S; Clinical Genetics Department, Human Genetics & Genome Research Division, Center of Excellence of Human Genetics, National Research Centre, Cairo, Egypt., Hosny GA; Department of Orthopedic Surgery, Banha University, Banha, Egypt., Otaify GA; Clinical Genetics Department, Human Genetics & Genome Research Division, Center of Excellence of Human Genetics, National Research Centre, Cairo, Egypt., Amr K; Clinical Genetics Department, Human Genetics & Genome Research Division, Center of Excellence of Human Genetics, National Research Centre, Cairo, Egypt., Al Tala S; Department of Pediatrics, Armed Forces Hospital Program Southwest Region, Khamis Mushait, Saudi Arabia., Khan AO; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Eye Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates., Rizk T; Department of Pediatric Neurology, Dr. Sulaiman Al Habib Hospital, Riyadh, Saudi Arabia., Alaqeel A; Department of Pediatric, Prince Sultan Medical Military City, Riyadh, Saudi Arabia., Alsiddiky A; Department of Orthopedics, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Singh A; Department of Pediatrics, Genetic Clinic, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India., Kapoor S; Department of Pediatrics, Maulana Azad Medical College, New Delhi, India., Alhashem A; Department of Pediatric, Prince Sultan Medical Military City, Riyadh, Saudi Arabia.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia., Faqeih E; Department of Pediatric Subspecialties, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia., Shaheen R; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. rshaheen@kfshrc.edu.sa., Alkuraya FS; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.; Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.; Department of Pediatric, Prince Sultan Medical Military City, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa. |
| المصدر: | Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2018 Dec; Vol. 20 (12), pp. 1609-1616. Date of Electronic Publication: 2018 Apr 05. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 9815831 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-0366 (Electronic) Linking ISSN: 10983600 NLM ISO Abbreviation: Genet Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2022- : [New York] : Elsevier Original Publication: Baltimore, MD : Lippincott, Williams & Wilkins, c1998- |
| مواضيع طبية MeSH: | Genetic Heterogeneity* , Genetic Predisposition to Disease*, Exome/*genetics , Musculoskeletal Abnormalities/*genetics, Alleles ; Blood Proteins/genetics ; Carboxylic Ester Hydrolases ; Cohort Studies ; Exoribonucleases/genetics ; Female ; Fetal Proteins/genetics ; Founder Effect ; Genetics, Population ; High-Throughput Nucleotide Sequencing ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Male ; Membrane Proteins/genetics ; Musculoskeletal Abnormalities/classification ; Musculoskeletal Abnormalities/pathology ; Neoplasm Proteins/genetics ; Oncogene Proteins/genetics ; Phenotype ; Receptors, Cell Surface/genetics ; Wnt3A Protein/genetics |
| مستخلص: | Purpose: To describe our experience with a large cohort (411 patients from 288 families) of various forms of skeletal dysplasia who were molecularly characterized. Methods: Detailed phenotyping and next-generation sequencing (panel and exome). Results: Our analysis revealed 224 pathogenic/likely pathogenic variants (54 (24%) of which are novel) in 123 genes with established or tentative links to skeletal dysplasia. In addition, we propose 5 genes as candidate disease genes with suggestive biological links (WNT3A, SUCO, RIN1, DIP2C, and PAN2). Phenotypically, we note that our cohort spans 36 established phenotypic categories by the International Skeletal Dysplasia Nosology, as well as 18 novel skeletal dysplasia phenotypes that could not be classified under these categories, e.g., the novel C3orf17-related skeletal dysplasia. We also describe novel phenotypic aspects of well-known disease genes, e.g., PGAP3-related Toriello-Carey syndrome-like phenotype. We note a strong founder effect for many genes in our cohort, which allowed us to calculate a minimum disease burden for the autosomal recessive forms of skeletal dysplasia in our population (7.16E-04), which is much higher than the global average. Conclusion: By expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions. |
| فهرسة مساهمة: | Keywords: Toriello–Carey; craniosynostosis; osteogenesis imperfecta |
| المشرفين على المادة: | 0 (Blood Proteins) 0 (DIP2C protein, human) 0 (Fetal Proteins) 0 (Intracellular Signaling Peptides and Proteins) 0 (LINC01565 protein, human) 0 (Membrane Proteins) 0 (Neoplasm Proteins) 0 (Oncogene Proteins) 0 (RIN1 protein, human) 0 (Receptors, Cell Surface) 0 (SUCO protein, human) 0 (WNT3A protein, human) 0 (Wnt3A Protein) EC 3.1.- (Exoribonucleases) EC 3.1.1.- (Carboxylic Ester Hydrolases) EC 3.1.1.- (PGAP3 protein, human) EC 3.1.13.4 (PAN2 protein, human) |
| تواريخ الأحداث: | Date Created: 20180406 Date Completed: 20190514 Latest Revision: 20220210 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1038/gim.2018.50 |
| PMID: | 29620724 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1530-0366 |
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| DOI: | 10.1038/gim.2018.50 |