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. 2021 Jun;65(6):577-588.
doi: 10.1111/jir.12835. Epub 2021 Mar 19.

Diagnostic yield of whole-exome sequencing in non-syndromic intellectual disability

E Z Taşkıran  1 , B Karaosmanoğlu  1 , C Koşukcu  1 , G Ürel-Demir  2 , Ö Akgün-Doğan  2 , P Ö Şimşek-Kiper  2 , M Alikaşifoğlu  1 , K Boduroğlu  2 , G E Utine  2
Affiliations

Diagnostic yield of whole-exome sequencing in non-syndromic intellectual disability

E Z Taşkıran et al. J Intellect Disabil Res. 2021 Jun.

Abstract

Background: Aetiological diagnosis in non-syndromic intellectual disability (NSID) still poses a diagnostic challenge to clinicians.

Methods: Screening is currently achieved by chromosomal microarrays followed by whole-exome sequencing (WES). In search for the aetiological yield of WES in patients with NSID, 59 unrelated patients were studied.

Results: Among the 59 patients, 44 (74.6%) were from consanguineous unions. Epilepsy was present in 11 (37.9%), behavioural problems in 12 (41.4%) and autistic features in 14 (48.3%). WES analysis resulted in molecular diagnosis in 29 patients (49.2%). Some of the genes were specific for nervous system functioning, like HERC1, TBC1D7, LINS, HECW2, DEAF1, HNMT, DLG3, NRXN1 and HUWE1. Others were ubiquitously expressed genes involved in fundamental cellular processes, like IARS, UBE3A, COQ4, TAF1, SETBP1, ARV1, ZC4H2, KAT6A, ASXL3, THOC6, HNRNPH2, TUBA8 and KIF1A. Twenty-two (75.8%) were consanguineously married; however, only 12 (41.4%) of the detected genes caused autosomal recessive phenotypes.

Conclusions: This cohort suggests that recessive genes probably represent an actually smaller subgroup of NSID, even among families with consanguinity. Although in societies with high consanguinity rates, considering the recessive inheritance first seems to be an advantageous strategy, de novo mutations in autosomal dominantly expressed genes represent the major aetiological group in patients with NSID, even among those patients from consanguineous families.

Keywords: consanguinity; diagnostic yield; non-syndromic intellectual disability; whole-exome sequencing.

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References

    1. Akawi N. A., Al-Jasmi F., Al-Shamsi A. M., Ali B. R., Al-Gazali L. (2013). LINS, a modulator of the WNT signaling pathway, is involved in human cognition. Orphanet Journal of Rare Diseases, 8, 87.
    1. Alfaiz A. A., Micale L., Mandriani B., Augello B., Pellico M. T., Chrast J. et al. (2014) TBC1D7 mutations are associated with intellectual disability, macrocrania, patellar dislocation, and celiac disease. Human Mutation 35, 447-451.
    1. Arboleda V. A., Lee H., Dorrani N., Zadeh N., Willis M., Macmurdo C. F. et al. (2015) De novo nonsense mutations in KAT6A, a lysine acetyl-transferase gene, cause a syndrome including microcephaly and global developmental delay. American Journal of Human Genetics 96, 498-506.
    1. Bachiller S., Rybkina T., Porras-García E., Pérez-Villegas E., Tabares L., Armengol J. A. et al. (2015) The HERC1 E3 ubiquitin ligase is essential for normal development and for neurotransmission at the mouse neuromuscular junction. Cellular and Molecular Life Sciences 72, 2961-2971.
    1. Bain J. M., Cho M. T., Telegrafi A., Wilson A., Brooks S., Botti C. et al. (2016) Variants in HNRNPH2 on the X chromosome are associated with a neurodevelopmental disorder in females. American Journal of Human Genetics 99, 728-734.

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