Accelerating Novel Candidate Gene Discovery in Neurogenetic Disorders via Whole-Exome Sequencing of Prescreened Multiplex Consanguineous Families

被引：356

作者：

Alazami, Anas M. ^{[1
]}

Patel, Nisha ^{[1
]}

Shamseldin, Hanan E. ^{[1
]}

Anazi, Shamsa ^{[1
]}

Al-Dosari, Mohammed S. ^{[2
]}

Alzahrani, Fatema ^{[1
]}

Hijazi, Hadia ^{[1
]}

Alshammari, Muneera ^{[3
,4
]}

Aldahmesh, Mohammed A. ^{[1
]}

Salih, Mustafa A. ^{[3
,4
]}

Faqeih, Eissa ^{[5
]}

Alhashem, Amal ^{[6
,7
]}

Bashiri, Fahad A. ^{[3
,4
]}

Al-Owain, Mohammed ^{[6
,8
]}

Kentab, Amal Y. ^{[3
,4
]}

Sogaty, Sameera ^{[9
]}

Al Tala, Saeed ^{[10
]}

Temsah, Mohamad-Hani ^{[3
,4
]}

Tulbah, Maha ^{[11
]}

Aljelaify, Rasha F. ^{[12
]}

Alshahwan, Saad A. ^{[7
]}

Seidahmed, Mohammed Zain ^{[13
]}

Alhadid, Adnan A. ^{[3
,4
]}

Aldhalaan, Hesham ^{[14
]}

AlQallaf, Fatema ^{[14
]}

Kurdi, Wesam ^{[11
]}

Alfadhel, Majid ^{[15
]}

Babay, Zainab ^{[16
]}

Alsogheer, Mohammad ^{[17
]}

Kaya, Namik ^{[1
]}

Al-Hassnan, Zuhair N. ^{[6
,8
]}

Abdel-Salam, Ghada M. H. ^{[18
]}

Al-Sannaa, Nouriya ^{[19
]}

Al Mutairi, Fuad ^{[15
]}

El Khashab, Heba Y. ^{[3
,4
,20
]}

Bohlega, Saeed ^{[14
]}

Jia, Xiaofei ^{[21
]}

Nguyen, Henry C. ^{[21
]}

Hammami, Rakad ^{[1
]}

Adly, Nouran ^{[1
]}

Mohamed, Jawahir Y. ^{[1
]}

Abdulwahab, Firdous ^{[1
]}

Ibrahim, Niema ^{[1
]}

Naim, Ewa A. ^{[1
,22
]}

Al-Younes, Banan ^{[1
,22
]}

Meyer, Brian F. ^{[1
,22
]}

Hashem, Mais ^{[1
]}

Shaheen, Ranad ^{[1
]}

Xiong, Yong ^{[21
]}

Abouelhoda, Mohamed ^{[1
,22
]}

机构：

[1] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia

[2] King Saud Univ, Coll Pharm, Dept Pharmacognosy, Riyadh 11451, Saudi Arabia

[3] King Saud Univ, King Khalid Univ Hosp, Dept Pediat, Riyadh 11451, Saudi Arabia

[4] King Saud Univ, Coll Med, Riyadh 11451, Saudi Arabia

[5] King Fahad Med City, Dept Pediat, Riyadh 11525, Saudi Arabia

[6] Alfaisal Univ, Coll Med, Dept Anat & Cell Biol, Riyadh 11533, Saudi Arabia

[7] Prince Sultan Mil Med City, Dept Pediat, Riyadh 11159, Saudi Arabia

[8] King Faisal Specialist Hosp & Res Ctr, Dept Med Genet, Riyadh 11211, Saudi Arabia

[9] King Fahad Gen Hosp, Dept Pediat, Jeddah 23325, Saudi Arabia

[10] Armed Forces Hosp, Dept Pediat, Khamis Mushayt 62413, Saudi Arabia

[11] King Faisal Specialist Hosp & Res Ctr, Dept Obstet & Gynecol, Riyadh 11211, Saudi Arabia

[12] King Abdulaziz City Sci & Technol, Ctr Excellence Genom, Riyadh 11442, Saudi Arabia

[13] Secur Forces Hosp, Dept Pediat, Riyadh 12625, Saudi Arabia

[14] King Faisal Specialist Hosp & Res Ctr, Dept Neurosci, Riyadh 11211, Saudi Arabia

[15] King Saud bin Abdulaziz Univ Hlth Sci, King Abdulaziz Med City, Dept Pediat, Div Genet, Riyadh 14611, Saudi Arabia

[16] King Saud Univ, Coll Med, Dept Obstet & Gynecol, Riyadh 11451, Saudi Arabia

[17] King Saud Univ, Coll Med, Dept Psychiat, Riyadh 11451, Saudi Arabia

[18] Natl Res Ctr, Human Genet & Genome Res Div, Dept Clin Genet, Cairo 12345, Egypt

[19] Johns Hopkins Aramco Healthcare, Dept Pediat, Dhahran 34465, Saudi Arabia

[20] Ain Shams Univ, Childrens Hosp, Dept Pediat, Cairo 01234, Egypt

[21] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA

[22] King Abdulaziz City Sci & Technol, Saudi Human Genome Program, Riyadh 11442, Saudi Arabia

[23] King Saud Univ, Coll Med, Dept Internal Med, Riyadh 11451, Saudi Arabia

来源：

CELL REPORTS | 2015年 / 10卷 / 02期

关键词：

NEURONAL MIGRATION; MENTAL-RETARDATION; GENOMIC ANALYSIS; MUTATIONS; REVEALS; DEFICIENCY; EPILEPSY; SUBUNIT; ONSET; MICE;

D O I：

10.1016/j.celrep.2014.12.015

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 pre-screening 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.

引用

页码：148 / 161

页数：14

共 40 条

[1] SET BINDING FACTOR 1 (SBF1) MUTATION CAUSES CHARCOT-MARIE-TOOTH DISEASE TYPE 4B3 [J].

Alazami, Anas M. ;

Alzahrani, Fatema ;

Bohlega, Saeed ;

Alkuraya, Fowzan S. .

NEUROLOGY, 2014, 82 (18) :1665-1666

[2]

Alkuraya F.S., 2012, CURR PROTOC HUM GENE, V6

[3] Homozygosity mapping: One more tool in the clinical geneticist's toolbox [J].

Alkuraya, Fowzan S. .

GENETICS IN MEDICINE, 2010, 12 (04) :236-239

[4] Deficiency in ubiquitin ligase TRIM2 causes accumulation of neurofilament light chain and neurodegeneration [J].

Balastik, Martin ;

Ferraguti, Francesco ;

Silva, Andre Pires-da ;

Lee, Tae Ho ;

Alvarez-Bolado, Gonzalo ;

Lu, Kun Ping ;

Gruss, Peter .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (33) :12016-12021

[5] Spindly/CCDC99 Is Required for Efficient Chromosome Congression and Mitotic Checkpoint Regulation [J].

Barisic, Marin ;

Sohm, Benedicte ;

Mikolcevic, Petra ;

Wandke, Cornelia ;

Rauch, Veronika ;

Ringer, Thomas ;

Hess, Michael ;

Bonn, Guenther ;

Geley, Stephan .

MOLECULAR BIOLOGY OF THE CELL, 2010, 21 (12) :1968-1981

[6] tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia [J].

Budde, Birgit S. ;

Namavar, Yasmin ;

Barth, Peter G. ;

Poll-The, Bwee Tien ;

Nuernberg, Gudrun ;

Becker, Christian ;

van Ruissen, Fred ;

Weterman, Marian A. J. ;

Fluiter, Kees ;

Beek, Erik T. te ;

Aronica, Eleonora ;

van der Knaap, Marjo S. ;

Hoehne, Wolfgang ;

Toliat, Mohammad Reza ;

Crow, Yanick J. ;

Steinlin, Maja ;

Voit, Thomas ;

Roelens, Filip ;

Brussel, Wim ;

Brockmann, Knut ;

Kyllerman, Marten ;

Boltshauser, Eugen ;

Hammersen, Gerhard ;

Willemsen, Michel ;

Basel-Vanagaite, Lina ;

Kraegeloh-Mann, Ingeborg ;

de Vries, Linda S. ;

Sztriha, Laszlo ;

Muntoni, Francesco ;

Ferrie, Colin D. ;

Battini, Roberta ;

Hennekam, Raoul C. M. ;

Grillo, Eugenio ;

Beemer, Frits A. ;

Stoets, Loes M. E. ;

Wollnik, Bernd ;

Nuernberg, Peter ;

Baas, Frank .

NATURE GENETICS, 2008, 40 (09) :1113-1118

[7] Autozygosity Mapping with Exome Sequence Data [J].

Carr, Ian M. ;

Bhaskar, Sanjeev ;

Sullivan, James O' ;

Aldahmesh, Mohammed A. ;

Shamseldin, Hanan E. ;

Markham, Alexander F. ;

Bonthron, David T. ;

Black, Graeme ;

Alkuraya, Fowzan S. .

HUMAN MUTATION, 2013, 34 (01) :50-56

[8] Pontocerebellar hypoplasia Clinical, pathologic, and genetic studies [J].

Cassandrini, D. ;

Biancheri, R. ;

Tessa, A. ;

Di Rocco, M. ;

Di Capua, M. ;

Bruno, C. ;

Denora, P. S. ;

Sartori, S. ;

Rossi, A. ;

Nozza, P. ;

Emma, F. ;

Mezzano, P. ;

Politi, M. R. ;

Laverda, A. M. ;

Zara, F. ;

Pavone, L. ;

Simonati, A. ;

Leuzzi, V. ;

Santorelli, F. M. ;

Bertini, E. .

NEUROLOGY, 2010, 75 (16) :1459-1464

[9] Microcephaly disease gene Wdr62 regulates mitotic progression of embryonic neural stem cells and brain size [J].

Chen, Jian-Fu ;

Zhang, Ying ;

Wilde, Jonathan ;

Hansen, Kirk C. ;

Lai, Fan ;

Niswander, Lee .

NATURE COMMUNICATIONS, 2014, 5

[10] A genetic model for neurodevelopmental disease [J].

Coe, Bradley P. ;

Girirajan, Santhosh ;

Eichler, Evan E. .

CURRENT OPINION IN NEUROBIOLOGY, 2012, 22 (05) :829-836

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