The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes

Dorota Monies; Mohamed Abouelhoda; Moeenaldeen AlSayed; Zuhair Alhassnan; Maha Alotaibi; Husam Kayyali; Mohammed Al-Owain; Ayaz Shah; Zuhair Rahbeeni; Mohammad A Al-Muhaizea; Hamad I Alzaidan; Edward Cupler; Saeed Bohlega; Eissa Faqeih; Maha Faden; Banan Alyounes; Dyala Jaroudi; Ewa Goljan; Hadeel Elbardisy; Asma Akilan; Renad Albar; Hesham Aldhalaan; Shamshad Gulab; Aziza Chedrawi; Bandar K Al Saud; Wesam Kurdi; Nawal Makhseed; Tahani Alqasim; Heba Y El Khashab; Hamoud Al-Mousa; Amal Alhashem; Imaduddin Kanaan; Talal Algoufi; Khalid Alsaleem; Talal A Basha; Fathiya Al-Murshedi; Sameena Khan; Adila Al-Kindy; Maha Alnemer; Sami Al-Hajjar; Suad Alyamani; Hasan Aldhekri; Ali Al-Mehaidib; Rand Arnaout; Omar Dabbagh; Mohammad Shagrani; Dieter Broering; Maha Tulbah; Amal Alqassmi; Maisoon Almugbel; Mohammed AlQuaiz; Abdulaziz Alsaman; Khalid Al-Thihli; Raashda A Sulaiman; Wajeeh Al-Dekhail; Abeer Alsaegh; Fahad A Bashiri; Alya Qari; Suzan Alhomadi; Hisham Alkuraya; Mohammed Alsebayel; Muddathir H Hamad; Laszlo Szonyi; Faisal Abaalkhail; Sulaiman M Al-Mayouf; Hamad Almojalli; Khalid S Alqadi; Hussien Elsiesy; Taghreed M Shuaib; Mohammed Zain Seidahmed; Ibraheem Abosoudah; Hana Akleh; Abdulaziz AlGhonaium; Turki M Alkharfy; Fuad Al Mutairi; Wafa Eyaid; Abdullah Alshanbary; Farrukh R Sheikh; Fahad I Alsohaibani; Abdullah Alsonbul; Saeed Al Tala; Soher Balkhy; Randa Bassiouni; Ahmed S Alenizi; Maged H Hussein; Saeed Hassan; Mohamed Khalil; Brahim Tabarki; Saad Alshahwan; Amira Oshi; Yasser Sabr; Saad Alsaadoun; Mustafa A Salih; Sarar Mohamed; Habiba Sultana; Abdullah Tamim; Moayad El-Haj; Saif Alshahrani; Dalal K Bubshait; Majid Alfadhel; Tariq Faquih; Mohamed El-Kalioby; Shazia Subhani; Zeeshan Shah; Nabil Moghrabi; Brian F Meyer; Fowzan S Alkuraya

doi:10.1007/s00439-017-1821-8

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The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes

Journal article

Open access

Peer reviewed

The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes

Dorota Monies, Mohamed Abouelhoda, Moeenaldeen AlSayed, Zuhair Alhassnan, Maha Alotaibi, Husam Kayyali, Mohammed Al-Owain, Ayaz Shah, Zuhair Rahbeeni, Mohammad A Al-Muhaizea, …

Human genetics, Vol.136(8), pp.921-939

01/08/2017

DOI: https://doi.org/10.1007/s00439-017-1821-8

PMCID: PMC5502059

PMID: 28600779

Abstract

Consanguinity

Exome

Female

Genetic Diseases, Inborn - diagnosis

Genetic Diseases, Inborn - epidemiology

Genetic Testing

Genome, Human

High-Throughput Nucleotide Sequencing

Homozygote

Humans

Male

Molecular Sequence Annotation

Morbidity

Mutation

Phenotype

Reproducibility of Results

Saudi Arabia - epidemiology

Sequence Analysis, DNA

In this study, we report the experience of the only reference clinical next-generation sequencing lab in Saudi Arabia with the first 1000 families who span a wide-range of suspected Mendelian phenotypes. A total of 1019 tests were performed in the period of March 2016-December 2016 comprising 972 solo (index only), 14 duo (parents or affected siblings only), and 33 trio (index and parents). Multigene panels accounted for 672 tests, while whole exome sequencing (WES) represented the remaining 347 tests. Pathogenic or likely pathogenic variants that explain the clinical indications were identified in 34% (27% in panels and 43% in exomes), spanning 279 genes and including 165 novel variants. While recessive mutations dominated the landscape of solved cases (71% of mutations, and 97% of which are homozygous), a substantial minority (27%) were solved on the basis of dominant mutations. The highly consanguineous nature of the study population also facilitated homozygosity for many private mutations (only 32.5% of the recessive mutations are founder), as well as the first instances of recessive inheritance of previously assumed strictly dominant disorders (involving ITPR1, VAMP1, MCTP2, and TBP). Surprisingly, however, dual molecular diagnosis was only observed in 1.5% of cases. Finally, we have encountered candidate variants in 75 genes (ABHD6, ACY3, ADGRB2, ADGRG7, AGTPBP1, AHNAK2, AKAP6, ASB3, ATXN1L, C17orf62, CABP1, CCDC186, CCP110, CLSTN2, CNTN3, CNTN5, CTNNA2, CWC22, DMAP1, DMKN, DMXL1, DSCAM, DVL2, ECI1, EP400, EPB41L5, FBXL22, GAP43, GEMIN7, GIT1, GRIK4, GRSF1, GTRP1, HID1, IFNL1, KCNC4, LRRC52, MAP7D3, MCTP2, MED26, MPP7, MRPS35, MTDH, MTMR9, NECAP2, NPAT, NRAP, PAX7, PCNX, PLCH2, PLEKHF1, PTPN12, QKI, RILPL2, RIMKLA, RIMS2, RNF213, ROBO1, SEC16A, SIAH1, SIRT2, SLAIN2, SLC22A20, SMDT1, SRRT, SSTR1, ST20, SYT9, TSPAN6, UBR4, VAMP4, VPS36, WDR59, WDYHV1, and WHSC1) not previously linked to human phenotypes and these are presented to accelerate post-publication matchmaking. Two of these genes were independently mutated in more than one family with similar phenotypes, which substantiates their link to human disease (AKAP6 in intellectual disability and UBR4 in early dementia). If the novel candidate disease genes in this cohort are independently confirmed, the yield of WES will have increased to 83%, which suggests that most "negative" clinical exome tests are unsolved due to interpretation rather than technical limitations.

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Title: The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes
Creators - without role: Dorota Monies - King Abdulaziz City for Science and Technology
Mohamed Abouelhoda - King Abdulaziz City for Science and Technology
Moeenaldeen AlSayed - Alfaisal University
Zuhair Alhassnan - Alfaisal University
Maha Alotaibi - King Saud Medical City
Husam Kayyali - King Faisal Specialist Hospital & Research Centre
Mohammed Al-Owain - King Faisal Specialist Hospital & Research Centre
Ayaz Shah - King Faisal Specialist Hospital & Research Centre
Zuhair Rahbeeni - King Faisal Specialist Hospital & Research Centre
Mohammad A Al-Muhaizea - Alfaisal University
Hamad I Alzaidan - Alfaisal University
Edward Cupler - King Faisal Specialist Hospital & Research Centre
Saeed Bohlega - King Faisal Specialist Hospital & Research Centre
Eissa Faqeih - King Fahd Medical City
Maha Faden - King Saud Medical City
Banan Alyounes - King Abdulaziz City for Science and Technology
Dyala Jaroudi - King Faisal Specialist Hospital & Research Centre
Ewa Goljan - King Faisal Specialist Hospital & Research Centre
Hadeel Elbardisy - King Faisal Specialist Hospital & Research Centre
Asma Akilan - King Faisal Specialist Hospital & Research Centre
Renad Albar - King Abdulaziz City for Science and Technology
Hesham Aldhalaan - King Faisal Specialist Hospital & Research Centre
Shamshad Gulab - King Faisal Specialist Hospital & Research Centre
Aziza Chedrawi - King Faisal Specialist Hospital & Research Centre
Bandar K Al Saud - Alfaisal University
Wesam Kurdi - King Faisal Specialist Hospital & Research Centre
Nawal Makhseed - Jahra Hospital
Tahani Alqasim - King Faisal Specialist Hospital & Research Centre
Heba Y El Khashab - Ain Shams University Hospital
Hamoud Al-Mousa - Alfaisal University
Amal Alhashem - Alfaisal University
Imaduddin Kanaan - King Faisal Specialist Hospital & Research Centre
Talal Algoufi - King Faisal Specialist Hospital & Research Centre
Khalid Alsaleem - King Faisal Specialist Hospital & Research Centre
Talal A Basha - King Faisal Specialist Hospital & Research Centre
Fathiya Al-Murshedi - Sultan Qaboos University Hospital
Sameena Khan - Alfaisal University
Adila Al-Kindy - Sultan Qaboos University Hospital
Maha Alnemer - King Faisal Specialist Hospital & Research Centre
Sami Al-Hajjar - King Faisal Specialist Hospital & Research Centre
Suad Alyamani - King Faisal Specialist Hospital & Research Centre
Hasan Aldhekri - Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Ali Al-Mehaidib - King Faisal Specialist Hospital & Research Centre
Rand Arnaout - King Faisal Specialist Hospital & Research Centre
Omar Dabbagh - King Faisal Specialist Hospital & Research Centre
Mohammad Shagrani - King Faisal Specialist Hospital & Research Centre
Dieter Broering - King Faisal Specialist Hospital & Research Centre
Maha Tulbah - King Faisal Specialist Hospital & Research Centre
Amal Alqassmi - King Saud Medical City
Maisoon Almugbel - King Faisal Specialist Hospital & Research Centre
Mohammed AlQuaiz - King Faisal Specialist Hospital & Research Centre
Abdulaziz Alsaman - National Neuroscience Institute
Khalid Al-Thihli - Sultan Qaboos University Hospital
Raashda A Sulaiman - King Faisal Specialist Hospital & Research Centre
Wajeeh Al-Dekhail - King Faisal Specialist Hospital & Research Centre
Abeer Alsaegh - Sultan Qaboos University Hospital
Fahad A Bashiri - King Saud University
Alya Qari - King Faisal Specialist Hospital & Research Centre
Suzan Alhomadi - King Saud Medical City
Hisham Alkuraya - Global Eye Care, Specialized Medical Center Hospital, Riyadh, Saudi Arabia
Mohammed Alsebayel - Department of Liver Transplantation, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Muddathir H Hamad - King Faisal Specialist Hospital & Research Centre
Laszlo Szonyi - Riyadh Armed Forces Hospital
Faisal Abaalkhail - Alfaisal University
Sulaiman M Al-Mayouf - King Faisal Specialist Hospital & Research Centre
Hamad Almojalli - Department of Liver Transplantation, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Khalid S Alqadi - King Faisal Specialist Hospital & Research Centre
Hussien Elsiesy - King Faisal Specialist Hospital & Research Centre
Taghreed M Shuaib - King Abdulaziz University
Mohammed Zain Seidahmed - Security Forces Hospital
Ibraheem Abosoudah - King Faisal Specialist Hospital & Research Centre
Hana Akleh - King Faisal Specialist Hospital & Research Centre
Abdulaziz AlGhonaium - Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Turki M Alkharfy - King Saud University
Fuad Al Mutairi - King Abdulaziz Medical City
Wafa Eyaid - King Saud bin Abdulaziz University for Health Sciences
Abdullah Alshanbary - Maternity and Children's Hospital
Farrukh R Sheikh - King Faisal Specialist Hospital & Research Centre
Fahad I Alsohaibani - King Faisal Specialist Hospital & Research Centre
Abdullah Alsonbul - King Faisal Specialist Hospital & Research Centre
Saeed Al Tala - Saudi German Hospital, Aseer, Saudi Arabia
Soher Balkhy - King Faisal Specialist Hospital & Research Centre
Randa Bassiouni - Taif University
Ahmed S Alenizi - King Saud Medical City
Maged H Hussein - King Faisal Specialist Hospital & Research Centre
Saeed Hassan - King Saud University
Mohamed Khalil - Department of Pediatrics, Dr. Suliman Al Habib Medical Group, Riyadh, Saudi Arabia
Brahim Tabarki - Riyadh Armed Forces Hospital
Saad Alshahwan - Riyadh Armed Forces Hospital
Amira Oshi - Neonatology, Al Hammadi Hospital, Riyadh, Saudi Arabia
Yasser Sabr - King Saud University
Saad Alsaadoun - Security Forces Hospital
Mustafa A Salih - King Saud University
Sarar Mohamed - Riyadh Armed Forces Hospital
Habiba Sultana - King Faisal Specialist Hospital & Research Centre
Abdullah Tamim - King Faisal Specialist Hospital & Research Centre
Moayad El-Haj - Medical Diagnostic Laboratory, Riyadh, Saudi Arabia
Saif Alshahrani - King Faisal Specialist Hospital & Research Centre
Dalal K Bubshait - King Fahd Hospital of the University
Majid Alfadhel - King Saud bin Abdulaziz University for Health Sciences
Tariq Faquih - King Abdulaziz City for Science and Technology
Mohamed El-Kalioby - King Abdulaziz City for Science and Technology
Shazia Subhani - King Abdulaziz City for Science and Technology
Zeeshan Shah - King Abdulaziz City for Science and Technology
Nabil Moghrabi - Medical Diagnostic Laboratory, Riyadh, Saudi Arabia
Brian F Meyer - King Abdulaziz City for Science and Technology
Fowzan S Alkuraya - King Abdulaziz City for Science and Technology
Publication Details: Human genetics, Vol.136(8), pp.921-939
Identifiers: 9913321308331
Academic Unit: King Faisal University; Alfaisal University; King Khalid University; King Abdulaziz University; King Saud University; King Abdulaziz City for Science & Technology; Imam Abdulrahman Bin Faisal University; King Saud Bin Abdulaziz University for Health Sciences
Language: English
Resource Type: Journal article