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10.3390/genes13030470
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Article

Complex Autism Spectrum Disorder with Epilepsy, Strabismus and Self-Injurious Behaviors in a Patient with a De Novo Heterozygous POLR2A Variant

by
Daniel R. Evans
1,
Ying Qiao
2,3,4,
Brett Trost
5,
Kristina Calli
2,3,4,
Sally Martell
2,3,4,
Steven J. M. Jones
2,4,6,
Stephen W. Scherer
5 and
M. E. Suzanne Lewis
2,3,4,*
1
Department of Family Practice, University of British Columbia (UBC), Victoria, BC V8R 1J8, Canada
2
Medical Genetics, University of British Columbia (UBC), Vancouver, BC V6H 3N1, Canada
3
BC Children’s Hospital Research Institute, Vancouver, BC V6H 3N1, Canada
4
iTARGET Autism, Vancouver, BC V6H 3N1, Canada
5
The Centre for Applied Genomics and McLaughlin Centre, Hospital for Sick Children, University of Toronto, Toronto, ON M5G 0A4, Canada
6
Michael Smith Genome Sciences Centre, Vancouver, BC V6H 3N1, Canada
*
Author to whom correspondence should be addressed.
Genes 2022, 13(3), 470; https://doi.org/10.3390/genes13030470
Submission received: 27 January 2022 / Revised: 28 February 2022 / Accepted: 3 March 2022 / Published: 7 March 2022
(This article belongs to the Special Issue Genetic and Phenotypic Subtypes of Autism Spectrum Disorder)
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Abstract

Autism spectrum disorder (ASD) describes a complex and heterogenous group of neurodevelopmental disorders. Whole genome sequencing continues to shed light on the multifactorial etiology of ASD. Dysregulated transcriptional pathways have been implicated in neurodevelopmental disorders. Emerging evidence suggests that de novo POLR2A variants cause a newly described phenotype called ‘Neurodevelopmental Disorder with Hypotonia and Variable Intellectual and Behavioral Abnormalities’ (NEDHIB). The variable phenotype manifests with a spectrum of features; primarily early onset hypotonia and delay in developmental milestones. In this study, we investigate a patient with complex ASD involving epilepsy and strabismus. Whole genome sequencing of the proband–parent trio uncovered a novel de novo POLR2A variant (c.1367T>C, p. Val456Ala) in the proband. The variant appears deleterious according to in silico tools. We describe the phenotype in our patient, who is now 31 years old, draw connections between the previously reported phenotypes and further delineate this emerging neurodevelopmental phenotype. This study sheds new insights into this neurodevelopmental disorder, and more broadly, the genetic etiology of ASD.
Keywords: POLR2A; autism spectrum disorder; neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities (NEDHIB); variant POLR2A; autism spectrum disorder; neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities (NEDHIB); variant

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MDPI and ACS Style

Evans, D.R.; Qiao, Y.; Trost, B.; Calli, K.; Martell, S.; Jones, S.J.M.; Scherer, S.W.; Lewis, M.E.S. Complex Autism Spectrum Disorder with Epilepsy, Strabismus and Self-Injurious Behaviors in a Patient with a De Novo Heterozygous POLR2A Variant. Genes 2022, 13, 470. https://doi.org/10.3390/genes13030470

AMA Style

Evans DR, Qiao Y, Trost B, Calli K, Martell S, Jones SJM, Scherer SW, Lewis MES. Complex Autism Spectrum Disorder with Epilepsy, Strabismus and Self-Injurious Behaviors in a Patient with a De Novo Heterozygous POLR2A Variant. Genes. 2022; 13(3):470. https://doi.org/10.3390/genes13030470

Chicago/Turabian Style

Evans, Daniel R., Ying Qiao, Brett Trost, Kristina Calli, Sally Martell, Steven J. M. Jones, Stephen W. Scherer, and M. E. Suzanne Lewis. 2022. "Complex Autism Spectrum Disorder with Epilepsy, Strabismus and Self-Injurious Behaviors in a Patient with a De Novo Heterozygous POLR2A Variant" Genes 13, no. 3: 470. https://doi.org/10.3390/genes13030470

APA Style

Evans, D. R., Qiao, Y., Trost, B., Calli, K., Martell, S., Jones, S. J. M., Scherer, S. W., & Lewis, M. E. S. (2022). Complex Autism Spectrum Disorder with Epilepsy, Strabismus and Self-Injurious Behaviors in a Patient with a De Novo Heterozygous POLR2A Variant. Genes, 13(3), 470. https://doi.org/10.3390/genes13030470

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