Novel Homozygous Full Gene Deletion of SLC12A5 in a Newborn With Refractory Seizures.

Abstract

SLC12A5 codes for a protein that mediates electroneutral potassium-chloride cotransport in mature neurons and is required to maintain chloride homeostasis in neurons. Pathogenic missense or truncating variants in SLC12A5 are associated with seizures and severe developmental impairment. Here, we describe a novel homozygous deletion (at least 50.3 kb) of SLC12A5 and NCOA5 genes in a neonate with refractory seizures identified by exome sequencing (ES). The proband was born at 30 weeks 4 days of gestation with a very low birth weight (1320 g), hypotonia, intractable refractory status epilepticus consistent with early infantile epileptiform encephalopathy, respiratory distress, multiple limb contractures, and dysmorphic facies. Confirmatory chromosome microarray analysis identified a ~86 kb homozygous deletion within a ~3 Mb long continuous stretch of homozygosity. The patient died at 5 days of age due to multiorgan failure subsequent to intractable status epilepticus. This is the first reported case of homozygous deletion of SLC12A5 that resulted in a live birth and demonstrates that SLC12A5 serves a critical role in muscle development, lung function, and neuronal function.