title: A novel de novo mutation in DYNC1H1 gene underlying malformation of cortical development and cataract.
abstract: 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.
authors.affiliation: Department of Paediatrics, Tawam Hospital, Al-Ain, United Arab Emirates.
authors.forename: Jozef
authors.initials: J
authors.lastname: Hertecant
authors.affiliation: Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
authors.forename: Makanko
authors.initials: M
authors.lastname: Komara
authors.affiliation: Department of Paediatrics, Tawam Hospital, Al-Ain, United Arab Emirates.
authors.forename: Aslam
authors.initials: A
authors.lastname: Nagi
authors.affiliation: Department of Paediatrics, Tawam Hospital, Al-Ain, United Arab Emirates; Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
authors.forename: Jehan
authors.initials: J
authors.lastname: Suleiman
authors.affiliation: Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
authors.forename: Lihadh
authors.initials: L
authors.lastname: Al-Gazali
authors.affiliation: Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
authors.forename: Bassam R
authors.initials: BR
authors.lastname: Ali
keywords: Cataract; Cortical malformation; DYNC1H1; Intellectual disability