Author(s):
Martins, M ; Oliveira, AR ; Martins, S ; Vieira, JP ; Perdigão, P ; Fernandes, AR ; de Almeida, LP ; Palma, PJ ; Sequeira, DB ; Santos, JM ; Duque, F ; Oliveira, G ; Cardoso, AL ; Peça, J ; Seabra, CM
Date: 2023
Persistent ID: http://hdl.handle.net/10400.17/4772
Origin: Repositório do Centro Hospitalar de Lisboa Central, EPE
Subject(s): Child; Cilia / genetics; DNA-Binding Proteins / genetics; Epilepsy* / genetics; Intellectual Disability* / genetics; Neurodevelopmental Disorders*; Seizures; HDE NEU PED
Description
Disruptions in the MBD5 gene have been linked with an array of clinical features such as global developmental delay, intellectual disability, autistic-like symptoms, and seizures, through unclear mechanisms. MBD5 haploinsufficiency has been associated with the disruption of primary cilium-related processes during early cortical development, and this has been reported in many neurodevelopmental disorders. In this study, we describe the clinical history of a 12-year-old child harboring a novel MBD5 rare variant and presenting psychomotor delay and seizures. To investigate the impact of MBD5 haploinsufficiency on neural primary cilia, we established a novel patient-derived cell line and used CRISPR-Cas9 technology to create an isogenic control. The patient-derived neural progenitor cells revealed a decrease in the length of primary cilia and in the total number of ciliated cells. This study paves the way to understanding the impact of MBD5 haploinsufficiency in brain development through its potential impact on neural primary cilia.
