Accelerating Novel Candidate Gene Discovery in Neurogenetic Disorders via Whole-Exome Sequencing of Prescreened Multiplex Consanguineous Families
Open accessAbstract
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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- Authors
- Alazami, A. M., Patel, N., Shamseldin, H. E., Anazi, S., Al-Dosari, M. S., Alzahrani, F., Hijazi, H., Alshammari, M., Aldahmesh, M. A., Salih, M. A., Faqeih, E., Alhashem, A., Bashiri, F. A., Al-Owain, M., Kentab, A. Y., Sogaty, S., Al Tala, S., Temsah, M.-H., Tulbah, M., Aljelaify, R. F., Alshahwan, S. A., Seidahmed, M. Z., Alhadid, A. A., Aldhalaan, H., AlQallaf, F., Kurdi, W., Alfadhel, M., Babay, Z., Alsogheer, M., Kaya, N., Al-Hassnan, Z. N., Abdel-Salam, G. M. H., Al-Sannaa, N., Al Mutairi, F., El Khashab, H. Y., Bohlega, S., Jia, X., Nguyen, H. C., Hammami, R., Adly, N., Mohamed, J. Y., Abdulwahab, F., Ibrahim, N., Naim, E. A., Al-Younes, B., Meyer, B. F., Hashem, M., Shaheen, R., Xiong, Y., Abouelhoda, M., Aldeeri, A. A., Monies, D. M., & Alkuraya, F. S.
- Affiliations
- King Faisal Specialist Hospital & Research Centre (SA)
- King Saud University (SA)
- King Fahd Medical City (SA)
- Riyadh Armed Forces Hospital (SA)
- King Fahad Hospital Jeddah (SA)
- King Abdulaziz City for Science and Technology (SA)
- Security Forces Hospital (SA)
- King Saud bin Abdulaziz University for Health Sciences (SA)
- Saudi Aramco Medical Services Organization (SA)
- Yale University (US)
- Corresponding author
- Alkuraya, Fowzan S.
- ORCID
- Alazami, Anas M.
- Shamseldin, Hanan E.
- Al-Dosari, Mohammed S.
- Hijazi, Hadia
- Aldahmesh, Mohammed A.
- Salih, Mustafa A.
- Faqeih, Eissa
- Alhashem, Amal
- Bashiri, Fahad A.
- Kentab, Amal Y.
- Temsah, Mohamad-Hani
- Tulbah, Maha
- Aljelaify, Rasha F.
- Seidahmed, Mohammed Zain
- Aldhalaan, Hesham
- Kurdi, Wesam
- Alfadhel, Majid
- Kaya, Namik
- Al-Sannaa, Nouriya
- Bohlega, Saeed
- Jia, Xiaofei
- Nguyen, Henry C.
- Meyer, Brian F.
- Shaheen, Ranad
- Xiong, Yong
- Abouelhoda, Mohamed
- Aldeeri, Abdulrahman A.
- Monies, Dorota M.
- Alkuraya, Fowzan S.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 10
- Issue
- 2
- Pages
- 148-161
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2098644602
- Cited by
- 465
- References
- 2
- Citations by year
- 2026: 25 · 2025: 43 · 2024: 29 · 2023: 39 · 2022: 45 · 2021: 42 · 2020: 48 · 2019: 38 · 2018: 42 · 2017: 39 · 2016: 46 · 2015: 27 · 2014: 1
- FWCI
- 24.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- neurogenetic disorders, candidate gene identification, consanguineous family, homozygosity mapping, multiplex families, novel disease genes, genotype-phenotype discordance, candidate gene association, exome sequencing
- MeSH terms
- Central Nervous System Diseases, Chromosome Mapping, Female, Homozygote, Humans, Male, Pedigree, Phenotype, Sequence Analysis, DNA, Polymorphism, Single Nucleotide, Genetic Association Studies, High-Throughput Nucleotide Sequencing
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