Author:
Bieder Andrea,Einarsdottir Elisabet,Matsson Hans,Nilsson Harriet E.,Eisfeldt Jesper,Dragomir Anca,Paucar Martin,Granberg Tobias,Li Tie-Qiang,Lindstrand Anna,Kere Juha,Tapia-Páez Isabel
Abstract
Abstract
Background
Developmental dyslexia (DD) is a neurodevelopmental learning disorder with high heritability. A number of candidate susceptibility genes have been identified, some of which are linked to the function of the cilium, an organelle regulating left-right asymmetry development in the embryo. Furthermore, it has been suggested that disrupted left-right asymmetry of the brain may play a role in neurodevelopmental disorders such as DD. However, it is unknown whether there is a common genetic cause to DD and laterality defects or ciliopathies.
Case presentation
Here, we studied two individuals with co-occurring situs inversus (SI) and DD using whole genome sequencing to identify genetic variants of importance for DD and SI. Individual 1 had primary ciliary dyskinesia (PCD), a rare, autosomal recessive disorder with oto-sino-pulmonary phenotype and SI. We identified two rare nonsynonymous variants in the dynein axonemal heavy chain 5 gene (DNAH5): a previously reported variant c.7502G > C; p.(R2501P), and a novel variant c.12043 T > G; p.(Y4015D). Both variants are predicted to be damaging. Ultrastructural analysis of the cilia revealed a lack of outer dynein arms and normal inner dynein arms. MRI of the brain revealed no significant abnormalities. Individual 2 had non-syndromic SI and DD. In individual 2, one rare variant (c.9110A > G;p.(H3037R)) in the dynein axonemal heavy chain 11 gene (DNAH11), coding for another component of the outer dynein arm, was identified.
Conclusions
We identified the likely genetic cause of SI and PCD in one individual, and a possibly significant heterozygosity in the other, both involving dynein genes. Given the present evidence, it is unclear if the identified variants also predispose to DD and further studies into the association between laterality, ciliopathies and DD are needed.
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics
Reference40 articles.
1. Deng H, Xia H, Deng S. Genetic basis of human left-right asymmetry disorders. Expert Rev Mol Med. 2015;16:e19.
2. Knowles MR, Zariwala M, Leigh M. Primary Ciliary dyskinesia. Clin Chest Med. 2016;37(3):449–61.
3. Hornef N, Olbrich H, Horvath J, et al. DNAH5 mutations are a common cause of primary ciliary dyskinesia with outer dynein arm defects. Am J Respir Crit Care Med. 2006;174(2):120–6.
4. Zariwala MAKM, Leigh MW. Primary Ciliary dyskinesia Seattle (WA). Seattle: University of Washington; 2007. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1122/. [updated 2019].
5. Gabel LA, Gibson CJ, Gruen JR, LoTurco JJ. Progress towards a cellular neurobiology of reading disability. Neurobiol Dis. 2010;38(2):173–80.
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