- 期刊
Identifying a Novel DCX Mutation in a Taiwanese Boy With Lissencephaly: A Case Report
摘要
Lissencephaly and subcortical band heterotopia are disorders associated with the failure of lamination of the six cortical layers. As a result, affected patients present with developmental delay and frequent epileptic seizures soon after birth. LIS1 and DCX are the two most commonly-affected genes in lissencephaly; the proteins encoded by both genes are involved in neuronal migration during brain development. In this report, we present a novel DCX mutation that has not been reported in the past. A 10-year-old Taiwanese boy was admitted to our pediatric neurology ward owing to a worsening mental status, refractory epileptic episodes, and a history of lissencephaly. With parental consent, a further genetic evaluation was performed. Screening of LIS1 by fluorescence in situ hybridization and whole-genome sequencing (WGS) yielded negative results; however, we identified a mutation in DCX that has never been reported. Subsequent in silico analyses confirmed that this mutation has a deleterious effect on the doublecortin protein. The patient's refractory epilepsy was managed by changing his anti-epileptic regimen from oxcarbazepine, phenobarbital, and valproic acid to a combination of levetiracetam, valproic acid, topiramate, and clonazepam. WGS revealed a novel missense mutation c.848A＞T (p.Lys283Met) of DCX. However, his family members declined genetic testing. While we were unable to determine whether this mutation was de novo or inherited through the patient's mother without further genetic testing, the discovery of this mutation is beneficial in terms of contributing to our knowledge of lissencephaly.