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

doi:10.1016/j.celrep.2014.12.015

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Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families

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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, …

Cell reports (Cambridge), Vol.10(2), pp.148-161

13/01/2015

DOI: https://doi.org/10.1016/j.celrep.2014.12.015

PMID: 25558065

Abstract

Central Nervous System Diseases - genetics

Central Nervous System Diseases - pathology

Chromosome Mapping

Female

Genetic Association Studies

High-Throughput Nucleotide Sequencing

Homozygote

Humans

Male

Pedigree

Phenotype

Polymorphism, Single Nucleotide

Sequence Analysis, DNA

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.

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Title: Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families
Creators - without role: 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 - King Saud University
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 - King Khalid University
Mohammed A Aldahmesh - Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
Mustafa A Salih - King Khalid University
Eissa Faqeih - Department of Pediatrics, King Fahad Medical City, Riyadh 11525, Saudi Arabia
Amal Alhashem - Alfaisal University
Fahad A Bashiri - King Khalid University
Mohammed Al-Owain - Alfaisal University
Amal Y Kentab - King Khalid University
Sameera Sogaty - Department of Pediatrics, King Fahad General Hospital, Jeddah 23325, Saudi Arabia
Saeed Al Tala - Armed Forces Hospital
Mohamad-Hani Temsah - King Khalid University
Maha Tulbah - Department of Obstetrics & Gynecology, King Faisal Specialist Hospital, Riyadh 11211, Saudi Arabia
Rasha F Aljelaify - King Abdulaziz City for Science and Technology
Saad A Alshahwan - Riyadh Armed Forces Hospital
Mohammed Zain Seidahmed - Security Forces Hospital
Adnan A Alhadid - King Khalid University Hospital
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 - King Saud bin Abdulaziz University for Health Sciences
Zainab Babay - King Saud University
Mohammad Alsogheer - King Saud University
Namik Kaya - Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
Zuhair N Al-Hassnan - Alfaisal University
Ghada M H Abdel-Salam - Department of Clinical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo 12345, Egypt
Nouriya Al-Sannaa - Johns Hopkins University
Fuad Al Mutairi - King Saud bin Abdulaziz University for Health Sciences
Heba Y El Khashab - King Khalid University
Saeed Bohlega - Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
Xiaofei Jia - Yale University
Henry C Nguyen - University of New Haven
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 - King Abdulaziz City for Science and Technology
Banan Al-Younes - King Abdulaziz City for Science and Technology
Brian F Meyer - King Abdulaziz City for Science and Technology
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 - Yale University
Mohamed Abouelhoda - King Abdulaziz City for Science and Technology
Abdulrahman A Aldeeri - King Saud University
Dorota M Monies - King Abdulaziz City for Science and Technology
Fowzan S Alkuraya - Alfaisal University
Publication Details: Cell reports (Cambridge), Vol.10(2), pp.148-161
Identifiers: 9913256608331
Academic Unit: Alfaisal University; King Khalid University; King Abdulaziz University; King Faisal University; King Saud University; King Abdulaziz City for Science & Technology; King Saud Bin Abdulaziz University for Health Sciences
Language: English
Resource Type: Journal article