Journal Article

DZNE-2020-01287

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery.

Hengel, H. (First author)DZNE* ; Buchert, R. ; Sturm, M. ; Haack, T. B. ; Schelling, Y. ; Mahajnah, M. ; Sharkia, R. ; Azem, A. ; Balousha, G. ; Ghanem, Z. ; Falana, M. ; Balousha, O. ; Ayesh, S. ; Keimer, R. ; Deigendesch, W. ; Zaidan, J. ; Marzouqa, H. ; Bauer, P. ; Schöls, L. (Last author)DZNE*

2020
Stockton Press Basingstoke

This record in other databases:    

Please use a persistent id in citations: doi:10.1038/s41431-020-0609-9

Abstract: 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.

Keyword(s): Arabs: genetics (MeSH) ; Female (MeSH) ; Gene Frequency (MeSH) ; Genetic Loci (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Nervous System Diseases: genetics (MeSH) ; Pedigree (MeSH) ; Exome Sequencing: standards (MeSH) ; Exome Sequencing: statistics & numerical data (MeSH)

---

Contributing Institute(s):

1. Parkinson Genetics (AG Gasser 1)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2020

---

Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---

---

Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) Hengel, H. (First author)DZNE* ; Buchert, R. ; Sturm, M. ; Haack, T. B. ; Schelling, Y.Extern* ; Mahajnah, M. ; Sharkia, R.Extern* ; Azem, A. ; Balousha, G. ; Ghanem, Z. ; Falana, M. ; Balousha, O. ; Ayesh, S. ; Keimer, R. ; Deigendesch, W. ; Zaidan, J. ; Marzouqa, H. ; Bauer, P. ; Schöls, L. (Last author)DZNE*
Correction to: First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery.
European journal of human genetics 30(2), 248 (2022) [10.1038/s41431-021-00909-7]2022   Files  Fulltext by Pubmed Central BibTeX | EndNote: XML, Text | RIS

---