Clinical and genetic analysis of PRRT2 gene mutations in a cohort of 21 pediatric patients: a case series
Abstract
Background: The Proline-Rich Transmembrane Protein 2 (PRRT2) gene is associated with a spectrum of autosomal dominant paroxysmal disorders, including Benign Familial Infantile Epilepsy (BFIE), Paroxysmal Kinesigenic Dyskinesia (PKD), and Hemiplegic Migraine (HM). However, the correlation between specific mutation types and clinical phenotypes, particularly for rare variants, remains to be fully elucidated.
Methods: We conducted a retrospective analysis of 21 pediatric patients (12 males, 9 females) with PRRT2-related disorders diagnosed at Xiamen Children's Hospital between June 2014 and December 2025. Clinical data were collected from electronic medical records. Genetic analysis was performed using family-based whole-exome sequencing. Variants were classified according to ACMG guidelines, and novel variants were assessed using bioinformatics tools (PolyPhen-2, PROVEAN, SIFT).
Results: The cohort included 14 patients with BFIE, 2 with non-BFIE epilepsy, 4 with PKD, and 1 with HM. Frameshift mutations were predominant (90.5%), with c.649dupC (p.Arg217Profs*8) being the most frequent (71.4%). A novel heterozygous missense variant, c.811C > T (p.Leu271Phe), was identified in a patient with drug-resistant focal epilepsy; in silico tools predicted it to be damaging. Functional analysis revealed that the intronic variant c.880-34G > A (p.?) causes aberrant mRNA splicing, leading to a premature termination codon (p.Ser294Leufs*29). The phenotypes demonstrated a temporal succession,…
How strong is the evidence?
Evidence Hub reads this as a case series, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health. Reported size: 21 participants or records.
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