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.

中文翻译：

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两名患有情景反转和发育障碍的个体中动力蛋白重链基因的罕见变体：一例病例报告。

背景技术发育障碍（DD）是一种具有高遗传力的神经发育学习障碍。已经鉴定出许多候选的易感基因，其中一些与纤毛的功能有关，纤毛是调节胚胎左右不对称发育的细胞器。此外，已经提出，大脑左右左右不对称的破坏可能在诸如DD之类的神经发育障碍中起作用。但是，尚不清楚是否存在引起DD和侧偏缺陷或纤毛病的常见遗传原因。案例介绍在这里，我们使用全基因组测序研究了两个同时发生位相反转（SI）和DD的个体，以确定对DD和SI重要的遗传变异。个体1患有原发性睫状运动障碍（PCD），这很罕见，具有耳中肺表型和SI的常染色体隐性遗传疾病。我们在动力蛋白轴突重链5基因（DNAH5）中发现了两个罕见的非同义变体：先前报道的变体c.7502G> C；p。（R2501P），和新的变体c.12043 T> G；第（Y4015D）页。预计这两种变体均具有破坏性。纤毛的超微结构分析显示，缺乏外部动力的臂和正常的内部动力的臂。大脑的MRI显示无明显异常。个体2具有非综合征性SI和DD。在个体2中，鉴定出在动力蛋白轴突重链11基因（DNAH11）中的一个罕见变体（c.9110A> G; p。（H3037R）），该蛋白编码动力蛋白轴外臂的另一部分。结论我们确定了一个人中SI和PCD的可能遗传原因，而另一个人中可能是重要的杂合性，两者都涉及动力蛋白基因。根据目前的证据，尚不清楚所鉴定的变体是否也易患DD，是否需要进一步研究侧位，纤毛病和DD之间的关系。