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A de novo splicing variant supports the candidacy of TLL1 in ASD pathogenesis

European Journal of Human Genetics volume 28, pages 525–528 (2020)Cite this article

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Abstract

Congenital heart disease (CHD) is the most common type of birth defects with family- and population-based studies supporting a strong hereditary component. Multifactorial inheritance is the rule although a growing number of Mendelian forms have been described including candidates that have yet to be confirmed independently. TLL1 is one such candidate that was proposed in the etiology of atrial septal defect (ASD). We describe a girl with congenitally corrected transposition of the great arteries (ccTGA) and ASD secundum whose whole-exome sequencing (WES) revealed a de novo splicing (c.1379-2A>G) variant in TLL1 as well as an inherited truncating variant in NODAL. The identification of this dual molecular diagnosis both supports the candidacy of TLL1 in ASD pathogenesis and highlights the power of WES in revealing multilocus cardiac phenotypes.

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Acknowledgements

We thank the study family for their enthusiastic participation. We thank Hessa Alsaif for her help with Fig. 1. This work was supported in part by King Salman Center for Disability Research (FSA).

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Authors and Affiliations

  1. Department of Pediatrics, Prince Sultan Military Medical City, Riyad, Saudi Arabia

    Talal Alanzi, Amal Alhashem & Fowzan S. Alkuraya

  2. College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

    Amal Alhashem & Fowzan S. Alkuraya

  3. Cardiac Center, Prince Sultan Military Medical City, Riyad, Saudi Arabia

    Khalid Dagriri

  4. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

    Fatema Alzahrani & Fowzan S. Alkuraya

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  1. Talal Alanzi
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  2. Amal Alhashem
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  3. Khalid Dagriri
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  4. Fatema Alzahrani
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  5. Fowzan S. Alkuraya
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Correspondence to Fowzan S. Alkuraya.

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Alanzi, T., Alhashem, A., Dagriri, K. et al. A de novo splicing variant supports the candidacy of TLL1 in ASD pathogenesis. Eur J Hum Genet 28, 525–528 (2020). https://doi.org/10.1038/s41431-019-0524-0

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