First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery

  1. Hengel, Holger ORCID logo
  2. Buchert, Rebecca ORCID logo
  3. Sturm, Marc
  4. Haack, Tobias B.
  5. Schelling, Yvonne
  6. Mahajnah, Muhammad
  7. Sharkia, Rajech
  8. Azem, Abdussalam
  9. Balousha, Ghassan
  10. Ghanem, Zaid
  11. falana, mohammed ORCID logo
  12. Balousha, Osama
  13. Ayesh, Suhail
  14. Keimer, Reinhard
  15. Deigendesch, Werner
  16. Zaidan, Jimmy
  17. Marzouqa, Hiyam
  18. Bauer, Peter ORCID logo
  19. Schöls, Ludger

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1000 Titel
  • First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery
1000 Autor/in
  1. Hengel, Holger |
  2. Buchert, Rebecca |
  3. Sturm, Marc |
  4. Haack, Tobias B. |
  5. Schelling, Yvonne |
  6. Mahajnah, Muhammad |
  7. Sharkia, Rajech |
  8. Azem, Abdussalam |
  9. Balousha, Ghassan |
  10. Ghanem, Zaid |
  11. falana, mohammed |
  12. Balousha, Osama |
  13. Ayesh, Suhail |
  14. Keimer, Reinhard |
  15. Deigendesch, Werner |
  16. Zaidan, Jimmy |
  17. Marzouqa, Hiyam |
  18. Bauer, Peter |
  19. Schöls, Ludger |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-03-25
1000 Erschienen in
1000 Quellenangabe
  • 28(8):1034-1043
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41431-020-0609-9 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382450/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • A high rate of consanguinity leads to a high prevalence of autosomal recessive disorders in inbred populations. One example of inbred populations is the Arab communities in Israel and the Palestinian Authority. In the Palestinian Authority in particular, due to limited access to specialized medical care, most patients do not receive a genetic diagnosis and can therefore neither receive genetic counseling nor possibly specific treatment. We used whole-exome sequencing as a first-line diagnostic tool in 83 Palestinian and Israeli Arab families with suspected neurogenetic disorders and were able to establish a probable genetic diagnosis in 51% of the families (42 families). Pathogenic, likely pathogenic or highly suggestive candidate variants were found in the following genes extending and refining the mutational and phenotypic spectrum of these rare disorders: ACO2, ADAT3, ALS2, AMPD2, APTX, B4GALNT1, CAPN1, CLCN1, CNTNAP1, DNAJC6, GAMT, GPT2, KCNQ2, KIF11, LCA5, MCOLN1, MECP2, MFN2, MTMR2, NT5C2, NTRK1, PEX1, POLR3A, PRICKLE1, PRKN, PRX, SCAPER, SEPSECS, SGCG, SLC25A15, SPG11, SYNJ1, TMCO1, and TSEN54. Further, this cohort has proven to be ideal for prioritization of new disease genes. Two separately published candidate genes (WWOX and PAX7) were identified in this study. Analyzing the runs of homozygosity (ROHs) derived from the Exome sequencing data as a marker for the rate of inbreeding, revealed significantly longer ROHs in the included families compared with a German control cohort. The total length of ROHs correlated with the detection rate of recessive disease-causing variants. Identification of the disease-causing gene led to new therapeutic options in four families.
1000 Sacherschließung
lokal Genetic Predisposition to Disease [MeSH]
lokal Female [MeSH]
lokal Humans [MeSH]
lokal Whole Exome Sequencing/statistics
lokal Genetics research
lokal Genetic Loci [MeSH]
lokal Arabs/genetics [MeSH]
lokal Article
lokal Pedigree [MeSH]
lokal Male [MeSH]
lokal Whole Exome Sequencing/standards [MeSH]
lokal Neurological disorders
lokal Nervous System Diseases/genetics [MeSH]
lokal Genetic testing
lokal Gene Frequency [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-9773-2667|https://orcid.org/0000-0001-7576-3326|https://frl.publisso.de/adhoc/uri/U3R1cm0sIE1hcmM=|https://frl.publisso.de/adhoc/uri/SGFhY2ssIFRvYmlhcyBCLg==|https://frl.publisso.de/adhoc/uri/U2NoZWxsaW5nLCBZdm9ubmU=|https://frl.publisso.de/adhoc/uri/TWFoYWpuYWgsIE11aGFtbWFk|https://frl.publisso.de/adhoc/uri/U2hhcmtpYSwgUmFqZWNo|https://frl.publisso.de/adhoc/uri/QXplbSwgQWJkdXNzYWxhbQ==|https://frl.publisso.de/adhoc/uri/QmFsb3VzaGEsIEdoYXNzYW4=|https://frl.publisso.de/adhoc/uri/R2hhbmVtLCBaYWlk|https://orcid.org/0000-0002-5893-8945|https://frl.publisso.de/adhoc/uri/QmFsb3VzaGEsIE9zYW1h|https://frl.publisso.de/adhoc/uri/QXllc2gsIFN1aGFpbA==|https://frl.publisso.de/adhoc/uri/S2VpbWVyLCBSZWluaGFyZA==|https://frl.publisso.de/adhoc/uri/RGVpZ2VuZGVzY2gsIFdlcm5lcg==|https://frl.publisso.de/adhoc/uri/WmFpZGFuLCBKaW1teQ==|https://frl.publisso.de/adhoc/uri/TWFyem91cWEsIEhpeWFt|https://orcid.org/0000-0001-9414-4555|https://frl.publisso.de/adhoc/uri/U2Now7ZscywgTHVkZ2Vy
1000 Hinweis
  • DeepGreen-ID: 09a5d37e726b4fe08c7a00bf55f59646 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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1000 Erstellt am 2023-11-18T17:11:30.677+0100
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1000 Zuletzt bearbeitet 2024-04-04T12:35:55.603+0200
1000 Objekt bearb. Thu Apr 04 12:35:55 CEST 2024
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