Expanding the phenome and variome of skeletal dysplasia

Sateesh Maddirevula; Saud Alsahli; Lamees Alhabeeb; Nisha Patel; Fatema Alzahrani; Hanan E. Shamseldin; Shams Anazi; Nour Ewida; Hessa S. Alsaif; Jawahir Y. Mohamed; Anas M. Alazami; Niema Ibrahim; Firdous Abdulwahab; Mais Hashem; Mohamed Abouelhoda; Dorota Monies; Nada Al Tassan; Muneera Alshammari; Afaf Alsagheir; Mohammed Zain Seidahmed; Samira Sogati; Mona S Aglan; Muddathir H. Hamad; Mustafa A. Salih; Ahlam A. Hamed; Nadia Alhashmi; Amira Nabil; Fatima Alfadli; Ghada M.H. Abdel-Salam; Hisham Alkuraya; Winnie Ong Peitee; W.T. Keng; Abdullah Qasem; Aziza M. Mushiba; Maha S Zaki; Mahmoud R. Fassad; Majid Alfadhel; Saji Alexander; Yasser Sabr; Samia Temtamy; Alka V Ekbote; Samira Ismail; Gamal Ahmed Hosny; Ghada A. Otaify; Khalda Amr; Saeed Al Tala; Arif O. Khan; Tamer Rizk; Aida Alaqeel; Abdulmonem Alsiddiky; Ankur Singh; Seema Kapoor; Amal Alhashem; Eissa Faqeih; Ranad Shaheen; Fowzan S. Alkuraya

doi:10.1038/gim.2018.50

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Expanding the phenome and variome of skeletal dysplasia

Journal article

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Peer reviewed

Expanding the phenome and variome of skeletal dysplasia

Sateesh Maddirevula, Saud Alsahli, Lamees Alhabeeb, Nisha Patel, Fatema Alzahrani, Hanan E. Shamseldin, Shams Anazi, Nour Ewida, Hessa S. Alsaif, Jawahir Y. Mohamed, …

Genetics in medicine, Vol.20(12), pp.1609-1616

12/2018

DOI: https://doi.org/10.1038/gim.2018.50

PMID: 29620724

Abstract

craniosynostosis

osteogenesis imperfecta

Toriello–Carey

To describe our experience with a large cohort (411 patients from 288 families) of various forms of skeletal dysplasia who were molecularly characterized. Detailed phenotyping and next-generation sequencing (panel and exome). 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. 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.

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Title: Expanding the phenome and variome of skeletal dysplasia
Creators - without role: Sateesh Maddirevula - King Faisal Specialist Hospital & Research Centre
Saud Alsahli - King Faisal Specialist Hospital & Research Centre
Lamees Alhabeeb - King Faisal Specialist Hospital & Research Centre
Nisha Patel - King Faisal Specialist Hospital & Research Centre
Fatema Alzahrani - King Faisal Specialist Hospital & Research Centre
Hanan E. Shamseldin - King Faisal Specialist Hospital & Research Centre
Shams Anazi - King Faisal Specialist Hospital & Research Centre
Nour Ewida - King Faisal Specialist Hospital & Research Centre
Hessa S. Alsaif - King Faisal Specialist Hospital & Research Centre
Jawahir Y. Mohamed - King Faisal Specialist Hospital & Research Centre
Anas M. Alazami - King Faisal Specialist Hospital & Research Centre
Niema Ibrahim - King Faisal Specialist Hospital & Research Centre
Firdous Abdulwahab - King Faisal Specialist Hospital & Research Centre
Mais Hashem - Department of Genetics King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia
Mohamed Abouelhoda - King Abdulaziz City for Science and Technology
Dorota Monies - King Abdulaziz City for Science and Technology
Nada Al Tassan - Department of Genetics King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia
Muneera Alshammari - King Saud University
Afaf Alsagheir - Audi
Mohammed Zain Seidahmed - Riyadh Armed Forces Hospital
Samira Sogati - King Fahad Hospital Jeddah
Mona S Aglan - National Research Centre
Muddathir H. Hamad - King Saud University
Mustafa A. Salih - King Saud University
Ahlam A. Hamed - University of Khartoum
Nadia Alhashmi - Department of Pediatrics Royal Hospital Muscat Oman
Amira Nabil - Alexandria University
Fatima Alfadli - Maternity and Children's Hospital
Ghada M.H. Abdel-Salam - National Research Centre
Hisham Alkuraya - Global Eye Care, Specialized Medical Center Hospital Riyadh Saudi Arabia
Winnie Ong Peitee - Hospital Kuala Lumpur
W.T. Keng - Hospital Kuala Lumpur
Abdullah Qasem - Riyadh Armed Forces Hospital
Aziza M. Mushiba - King Fahd Medical City
Maha S Zaki - National Research Centre
Mahmoud R. Fassad - Alexandria University
Majid Alfadhel - King Saud bin Abdulaziz University for Health Sciences
Saji Alexander - Chelsea and Westminster Hospital NHS Foundation Trust
Yasser Sabr - King Saud University
Samia Temtamy - National Research Centre
Alka V Ekbote - Christian Medical College & Hospital
Samira Ismail - National Research Centre
Gamal Ahmed Hosny - Benha University
Ghada A. Otaify - National Research Centre
Khalda Amr - National Research Centre
Saeed Al Tala - Armed Forces Hospital
Arif O. Khan - King Faisal Specialist Hospital & Research Centre
Tamer Rizk - Department of Pediatric Neurology Dr. Sulaiman Al Habib Hospital Riyadh Saudi Arabia
Aida Alaqeel - Riyadh Armed Forces Hospital
Abdulmonem Alsiddiky - King Saud University
Ankur Singh - Institute of Medical Sciences
Seema Kapoor - Maulana Azad Medical College
Amal Alhashem - Alfaisal University
Eissa Faqeih - King Fahd Medical City
Ranad Shaheen - Department of Genetics King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia
Fowzan S. Alkuraya - King Faisal Specialist Hospital & Research Centre
Publication Details: Genetics in medicine, Vol.20(12), pp.1609-1616
Publisher: Elsevier Inc
Identifiers: 9913244608331
Academic Unit: Alfaisal University; King Khalid University; King Faisal University; King Saud University; King Saud Bin Abdulaziz University for Health Sciences
Language: English
Resource Type: Journal article