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A homozygous deletion of PLCB1 was identified by array CGH in a single consanguineous proband with malignant migrating partial seizures of infancy (MMPEI), disrupting the promoter and first three coding exons and predicting loss of function (PMID:22690784). No additional PLCB1 mutations were found in six further MMPEI cases (PMID:24315024). Functional concordance is supported by a Plcb1 knockout mouse model exhibiting early-onset epilepsy analogous to the human phenotype. Despite this experimental evidence, the genetic data remain limited to a single family without segregation beyond the proband, and negative screening in other cohorts.
Key Take-home: PLCB1 loss of function may underlie MMPEI in rare families, but broader genetic validation is required before routine diagnostic screening.
Gene–Disease AssociationLimitedSingle homozygous proband; no segregation beyond the proband; negative screening in six additional cases Genetic EvidenceLimitedOne reported homozygous deletion in a consanguineous family; no further segregation data; absence of variants in six additional patients Functional EvidenceModeratePlcb1 knockout mouse model recapitulates early-onset epileptic phenotype |