Cell Reports (Jan 2015)
Accelerating Novel Candidate Gene Discovery in Neurogenetic Disorders via Whole-Exome Sequencing of Prescreened Multiplex Consanguineous Families
- Anas M. Alazami,
- Nisha Patel,
- Hanan E. Shamseldin,
- Shamsa Anazi,
- Mohammed S. Al-Dosari,
- Fatema Alzahrani,
- Hadia Hijazi,
- Muneera Alshammari,
- Mohammed A. Aldahmesh,
- Mustafa A. Salih,
- Eissa Faqeih,
- Amal Alhashem,
- Fahad A. Bashiri,
- Mohammed Al-Owain,
- Amal Y. Kentab,
- Sameera Sogaty,
- Saeed Al Tala,
- Mohamad-Hani Temsah,
- Maha Tulbah,
- Rasha F. Aljelaify,
- Saad A. Alshahwan,
- Mohammed Zain Seidahmed,
- Adnan A. Alhadid,
- Hesham Aldhalaan,
- Fatema AlQallaf,
- Wesam Kurdi,
- Majid Alfadhel,
- Zainab Babay,
- Mohammad Alsogheer,
- Namik Kaya,
- Zuhair N. Al-Hassnan,
- Ghada M.H. Abdel-Salam,
- Nouriya Al-Sannaa,
- Fuad Al Mutairi,
- Heba Y. El Khashab,
- Saeed Bohlega,
- Xiaofei Jia,
- Henry C. Nguyen,
- Rakad Hammami,
- Nouran Adly,
- Jawahir Y. Mohamed,
- Firdous Abdulwahab,
- Niema Ibrahim,
- Ewa A. Naim,
- Banan Al-Younes,
- Brian F. Meyer,
- Mais Hashem,
- Ranad Shaheen,
- Yong Xiong,
- Mohamed Abouelhoda,
- Abdulrahman A. Aldeeri,
- Dorota M. Monies,
- Fowzan S. Alkuraya
Affiliations
- Anas M. Alazami
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Nisha Patel
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Hanan E. Shamseldin
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Shamsa Anazi
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Mohammed S. Al-Dosari
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
- Fatema Alzahrani
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Hadia Hijazi
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Muneera Alshammari
- Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
- Mohammed A. Aldahmesh
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Mustafa A. Salih
- Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
- Eissa Faqeih
- Department of Pediatrics, King Fahad Medical City, Riyadh 11525, Saudi Arabia
- Amal Alhashem
- Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
- Fahad A. Bashiri
- Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
- Mohammed Al-Owain
- Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
- Amal Y. Kentab
- Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
- Sameera Sogaty
- Department of Pediatrics, King Fahad General Hospital, Jeddah 23325, Saudi Arabia
- Saeed Al Tala
- Department of Pediatrics, Armed Forces Hospital, Khamis Mushayt 62413, Saudi Arabia
- Mohamad-Hani Temsah
- Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
- Maha Tulbah
- Department of Obstetrics & Gynecology, King Faisal Specialist Hospital, Riyadh 11211, Saudi Arabia
- Rasha F. Aljelaify
- Center of Excellence for Genomics, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia
- Saad A. Alshahwan
- Department of Pediatrics, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia
- Mohammed Zain Seidahmed
- Department of Pediatrics, Security Forces Hospital, Riyadh 12625, Saudi Arabia
- Adnan A. Alhadid
- Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
- Hesham Aldhalaan
- Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Fatema AlQallaf
- Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Wesam Kurdi
- Department of Obstetrics & Gynecology, King Faisal Specialist Hospital, Riyadh 11211, Saudi Arabia
- Majid Alfadhel
- Division of Genetics, Department of Pediatrics, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh 14611, Saudi Arabia
- Zainab Babay
- Department of Obstetrics and Gynecology, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
- Mohammad Alsogheer
- Department of Psychiatry, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
- Namik Kaya
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Zuhair N. Al-Hassnan
- Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
- Ghada M.H. Abdel-Salam
- Department of Clinical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo 12345, Egypt
- Nouriya Al-Sannaa
- Department of Pediatrics, Johns Hopkins Aramco Healthcare, Dhahran 34465, Saudi Arabia
- Fuad Al Mutairi
- Division of Genetics, Department of Pediatrics, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh 14611, Saudi Arabia
- Heba Y. El Khashab
- Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
- Saeed Bohlega
- Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Xiaofei Jia
- Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
- Henry C. Nguyen
- Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
- Rakad Hammami
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Nouran Adly
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Jawahir Y. Mohamed
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Firdous Abdulwahab
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Niema Ibrahim
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Ewa A. Naim
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Banan Al-Younes
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Brian F. Meyer
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Mais Hashem
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Ranad Shaheen
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Yong Xiong
- Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
- Mohamed Abouelhoda
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Abdulrahman A. Aldeeri
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Dorota M. Monies
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- Fowzan S. Alkuraya
- Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
- DOI
- https://doi.org/10.1016/j.celrep.2014.12.015
- Journal volume & issue
-
Vol. 10,
no. 2
pp. 148 – 161
Abstract
Our knowledge of disease genes in neurological disorders is incomplete. With the aim of closing this gap, we performed whole-exome sequencing on 143 multiplex consanguineous families in whom known disease genes had been excluded by autozygosity mapping and candidate gene analysis. This prescreening step led to the identification of 69 recessive genes not previously associated with disease, of which 33 are here described (SPDL1, TUBA3E, INO80, NID1, TSEN15, DMBX1, CLHC1, C12orf4, WDR93, ST7, MATN4, SEC24D, PCDHB4, PTPN23, TAF6, TBCK, FAM177A1, KIAA1109, MTSS1L, XIRP1, KCTD3, CHAF1B, ARV1, ISCA2, PTRH2, GEMIN4, MYOCD, PDPR, DPH1, NUP107, TMEM92, EPB41L4A, and FAM120AOS). We also encountered instances in which the phenotype departed significantly from the established clinical presentation of a known disease gene. Overall, a likely causal mutation was identified in >73% of our cases. This study contributes to the global effort toward a full compendium of disease genes affecting brain function.
