Alazami Anas M, Patel Nisha, Shamseldin Hanan E, Anazi Shamsa, Al-Dosari Mohammed S, Alzahrani Fatema, Hijazi Hadia, Alshammari Muneera, Aldahmesh Mohammed A, Salih Mustafa A, Faqeih Eissa, Alhashem Amal, Bashiri Fahad A, Al-Owain Mohammed, Kentab Amal Y, Sogaty Sameera, Al Tala Saeed, Temsah Mohamad-Hani, Tulbah Maha, Aljelaify Rasha F, Alshahwan Saad A, Seidahmed Mohammed Zain, Alhadid Adnan A, Aldhalaan Hesham, AlQallaf Fatema, Kurdi Wesam, Alfadhel Majid, Babay Zainab, Alsogheer Mohammad, Kaya Namik, Al-Hassnan Zuhair N, Abdel-Salam Ghada M H, Al-Sannaa Nouriya, Al Mutairi Fuad, El Khashab Heba Y, Bohlega Saeed, Jia Xiaofei, Nguyen Henry C, Hammami Rakad, Adly Nouran, Mohamed Jawahir Y, Abdulwahab Firdous, Ibrahim Niema, Naim Ewa A, Al-Younes Banan, Meyer Brian F, Hashem Mais, Shaheen Ranad, Xiong Yong, Abouelhoda Mohamed, Aldeeri Abdulrahman A, Monies Dorota M, Alkuraya Fowzan S
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Cell Rep. 2015 Jan 13;10(2):148-61. doi: 10.1016/j.celrep.2014.12.015. Epub 2014 Dec 31.
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.
我们对神经疾病相关致病基因的了解并不完整。为了填补这一空白，我们对143个多重近亲家庭进行了全外显子组测序，这些家庭通过纯合性定位和候选基因分析已排除已知致病基因。这一预筛选步骤使得我们鉴定出69个此前未与疾病相关联的隐性基因，本文描述了其中33个基因（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和FAM120AOS）。我们还遇到了一些情况，即表型与已知致病基因既定的临床表现存在显著差异。总体而言，我们在超过73%的病例中鉴定出了可能的致病突变。这项研究有助于全球致力于全面汇编影响脑功能的致病基因。
