Hertecant Jozef, Komara Makanko, Nagi Aslam, Suleiman Jehan, Al-Gazali Lihadh, Ali Bassam R
Department of Paediatrics, Tawam Hospital, Al-Ain, United Arab Emirates.
Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
Meta Gene. 2016 May 18;9:124-7. doi: 10.1016/j.mgene.2016.05.004. eCollection 2016 Sep.
Mutations in DYNC1H1, the gene encoding the largest cytoplasmic dynein, have been associated with a wide spectrum of neurodegenerative disorders. In this study, we describe a child in whom a novel de novo likely pathogenic variant in the motor domain of DYCN1H1 was identified through whole exome sequencing. The affected child presented with severe neurological symptoms and more extensive cortical malformations compared to previously reported cases with mutations in this gene, including diffuse pachygyria-lissencephaly and bilateral symmetric subcortical gray matter heterotopia. A more distinct aspect of the phenotype in this child is the presence of cataract in infancy. So far, only acquired bilateral cataract in adulthood has been described in this disorder in a patient with a much milder neurological phenotype. These findings could extend the phenotype associated with defective DYNC1H1 and suggest a possible important role in human ocular development.
编码最大胞质动力蛋白的基因 DYNC1H1 发生突变，与多种神经退行性疾病有关。在本研究中，我们描述了一名儿童，通过全外显子组测序在其体内鉴定出一种位于 DYCN1H1 运动结构域的新型新生可能致病变异。与先前报道的该基因突变病例相比，这名患病儿童表现出严重的神经症状和更广泛的皮质畸形，包括弥漫性巨脑回-无脑回畸形和双侧对称性皮质下灰质异位。该患儿表型中一个更独特的方面是婴儿期出现白内障。到目前为止，在这种疾病中，仅在一名神经表型温和得多的成年患者中描述过后天性双侧白内障。这些发现可能会扩展与 DYNC1H1 缺陷相关的表型，并提示其在人类眼部发育中可能发挥重要作用。
