Type
ArticleAuthors
Anazi, ShamsMaddirevula, Sateesh
Salpietro, Vincenzo
Asi, Yasmine T.
Alsahli, Saud
Alhashem, Amal
Shamseldin, Hanan E.
AlZahrani, Fatema
Patel, Nisha
Ibrahim, Niema
Abdulwahab, Firdous M.
Hashem, Mais
Alhashmi, Nadia
Al Murshedi, Fathiya
Al Kindy, Adila
Alshaer, Ahmad
Rumayyan, Ahmed
Al Tala, Saeed
Kurdi, Wesam

Alsaman, Abdulaziz
Alasmari, Ali
Banu, Selina
Sultan, Tipu
Saleh, Mohammed M.
Alkuraya, Hisham
Salih, Mustafa A.
Aldhalaan, Hesham
Ben-Omran, Tawfeg
Al Musafri, Fatima
Ali, Rehab
Suleiman, Jehan
Tabarki, Brahim
El-Hattab, Ayman W.
Bupp, Caleb
Alfadhel, Majid
Al Tassan, Nada
Monies, Dorota

Arold, Stefan T.

Abouelhoda, Mohamed
Lashley, Tammaryn
Houlden, Henry
Faqeih, Eissa
Alkuraya, Fowzan S.

KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Computational Bioscience Research Center (CBRC)
Date
2017-09-22Online Publication Date
2017-09-22Print Publication Date
2017-11Embargo End Date
2018-09-22Permanent link to this record
http://hdl.handle.net/10754/625777
Metadata
Show full item recordAbstract
Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms.Citation
Anazi S, Maddirevula S, Salpietro V, Asi YT, Alsahli S, et al. (2017) Expanding the genetic heterogeneity of intellectual disability. Human Genetics. Available: http://dx.doi.org/10.1007/s00439-017-1843-2.Sponsors
We thank the study families for their enthusiastic participation. This work was supported in part by King Salman Center for Disability Research (FSA). We acknowledge the support of the Saudi Human Genome Program and the Sequencing and Genotyping Core Facilities at KFSRHC. The research by STA reported in this publication was supported by funding from King Abdullah University of Science and Technology (KAUST).Publisher
Springer Science and Business Media LLCJournal
Human GeneticsPubMed ID
28940097Additional Links
https://link.springer.com/article/10.1007%2Fs00439-017-1843-2https://discovery.ucl.ac.uk/1576522/3/Lashley_Anazi%20S%20et%20al.pdf
ae974a485f413a2113503eed53cd6c53
10.1007/s00439-017-1843-2
Scopus Count
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