Phenotypic and genotypic characterization of NPRL3‐related epilepsy: Two case reports and literature review

Abstract

Nitrogen permease regulator‐like 3 (NPRL3) has been reported to play a role in seizure onset. The principal manifestation of NPRL3‐related epilepsy is a range of epilepsy‐associated syndromes, such as familial focal epilepsy with variable foci (FFEVF), sleep‐related hypermotor epilepsy (SHE), and temporal lobe epilepsy (TLE). The association between phenotype and genotype of NPRL3 mutations remains inadequately described. This study aimed to explore the phenotypic and genotypic spectra of NPRL3‐related epilepsy. We reported two novel NPRL3 variants in two unrelated epilepsy cases, including a nonsense (c.1174C>T, p.Gln392*) and a missense variant (c.1322C>T, p.Thr441Met). Following a review of the literature, a total of 116 cases of NPRL3‐related epilepsy were assessed, mostly with nonsense and frameshift mutations. Our findings suggest that patients harboring various NPRL3 variants exhibit variable clinical manifestations. In addition, it may be worthwhile to consider the existence of NPRL3 mutations in epilepsy patients with a family history. This study provides useful information for the treatment and prognosis by expanding the phenotypic and genotypic spectrum of NPRL3‐related epilepsy.