Ben-Omran T

References (2)

Title : Autozygome and high throughput confirmation of disease genes candidacy - Maddirevula_2019_Genet.Med_21_736
Author(s) : Maddirevula S , Alzahrani F , Al-Owain M , Al Muhaizea MA , Kayyali HR , AlHashem A , Rahbeeni Z , Al-Otaibi M , Alzaidan HI , Balobaid A , El Khashab HY , Bubshait DK , Faden M , Yamani SA , Dabbagh O , Al-Mureikhi M , Jasser AA , Alsaif HS , Alluhaydan I , Seidahmed MZ , Alabbasi BH , Almogarri I , Kurdi W , Akleh H , Qari A , Al Tala SM , Alhomaidi S , Kentab AY , Salih MA , Chedrawi A , Alameer S , Tabarki B , Shamseldin HE , Patel N , Ibrahim N , Abdulwahab F , Samira M , Goljan E , Abouelhoda M , Meyer BF , Hashem M , Shaheen R , AlShahwan S , Alfadhel M , Ben-Omran T , Al-Qattan MM , Monies D , Alkuraya FS
Ref : Genet Med , 21 :736 , 2019
Abstract : PURPOSE: Establishing links between Mendelian phenotypes and genes enables the proper interpretation of variants therein. Autozygome, a rich source of homozygous variants, has been successfully utilized for the high throughput identification of novel autosomal recessive disease genes. Here, we highlight the utility of the autozygome for the high throughput confirmation of previously published tentative links to diseases. METHODS: Autozygome and exome analysis of patients with suspected Mendelian phenotypes. All variants were classified according to the American College of Medical Genetics and Genomics guidelines. RESULTS: We highlight 30 published candidate genes (ACTL6B, ADAM22, AGTPBP1, APC, C12orf4, C3orf17 (NEPRO), CENPF, CNPY3, COL27A1, DMBX1, FUT8, GOLGA2, KIAA0556, LENG8, MCIDAS, MTMR9, MYH11, QRSL1, RUBCN, SLC25A42, SLC9A1, TBXT, TFG, THUMPD1, TRAF3IP2, UFC1, UFM1, WDR81, XRCC2, ZAK) in which we identified homozygous likely deleterious variants in patients with compatible phenotypes. We also identified homozygous likely deleterious variants in 18 published candidate genes (ABCA2, ARL6IP1, ATP8A2, CDK9, CNKSR1, DGAT1, DMXL2, GEMIN4, HCN2, HCRT, MYO9A, PARS2, PLOD3, PREPL, SCLT1, STX3, TXNRD2, WIPI2) although the associated phenotypes are sufficiently different from the original reports that they represent phenotypic expansion or potentially distinct allelic disorders. CONCLUSIONS: Our results should facilitate the timely relabeling of these candidate disease genes in relevant databases to improve the yield of clinical genomic sequencing.
ESTHER : Maddirevula_2019_Genet.Med_21_736
PubMedSearch : Maddirevula_2019_Genet.Med_21_736
PubMedID: 30237576

Title : Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders - Novarino_2014_Science_343_506
Author(s) : Novarino G , Fenstermaker AG , Zaki MS , Hofree M , Silhavy JL , Heiberg AD , Abdellateef M , Rosti B , Scott E , Mansour L , Masri A , Kayserili H , Al-Aama JY , Abdel-Salam GMH , Karminejad A , Kara M , Kara B , Bozorgmehri B , Ben-Omran T , Mojahedi F , El Din Mahmoud IG , Bouslam N , Bouhouche A , Benomar A , Hanein S , Raymond L , Forlani S , Mascaro M , Selim L , Shehata N , Al-Allawi N , Bindu PS , Azam M , Gunel M , Caglayan A , Bilguvar K , Tolun A , Issa MY , Schroth J , Spencer EG , Rosti RO , Akizu N , Vaux KK , Johansen A , Koh AA , Megahed H , Durr A , Brice A , Stevanin G , Gabriel SB , Ideker T , Gleeson JG
Ref : Science , 343 :506 , 2014
Abstract : Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease.
ESTHER : Novarino_2014_Science_343_506
PubMedSearch : Novarino_2014_Science_343_506
PubMedID: 24482476