Rare variants in dynein heavy chain genes in two individuals with situs inversus and developmental dyslexia : a case report
| Autor: | Martin Paucar, Anca Dragomir, Tie-Qiang Li, Harriet Nilsson, Elisabet Einarsdottir, Juha Kere, Anna Lindstrand, Tobias Granberg, Hans Matsson, Andrea Bieder, Jesper Eisfeldt, Isabel Tapia-Páez |
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| Přispěvatelé: | Biosciences, Päivi Marjaana Saavalainen / Principal Investigator, STEMM - Stem Cells and Metabolism Research Program, Juha Kere / Principal Investigator, Research Programs Unit, HUS Helsinki and Uusimaa Hospital District, University of Helsinki, Biosciences, University of Helsinki, STEMM - Stem Cells and Metabolism Research Program |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Nonsynonymous substitution Male Candidate gene L-R asymmetry defects NEUROBIOLOGY Case Report Ciliopathies CANDIDATE GENES Dyslexia 0302 clinical medicine Child Genetics (clinical) Primary ciliary dyskinesia Genetics Cilium 1184 Genetics developmental biology physiology Brain DYX1C1 Middle Aged Situs Inversus Situs inversus Female Medical Genetics Ciliary Motility Disorders lcsh:Internal medicine Heterozygote lcsh:QH426-470 GENETICS Developmental dyslexia Dynein HANDEDNESS Brain imaging Biology Polymorphism Single Nucleotide 03 medical and health sciences medicine Humans Genetic Predisposition to Disease lcsh:RC31-1245 Medicinsk genetik DCDC2 MUTATIONS CAUSE Dyneins Axonemal Dyneins medicine.disease lcsh:Genetics 030104 developmental biology Whole genome sequencing Mutation SNVs 3111 Biomedicine Outer dynein arm 030217 neurology & neurosurgery |
| Zdroj: | BMC Medical Genetics BMC Medical Genetics, Vol 21, Iss 1, Pp 1-9 (2020) |
| Popis: | BackgroundDevelopmental 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 presentationHere, we studied two individuals with co-occurringsitus 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.ConclusionsWe 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. |
| Databáze: | OpenAIRE |
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