Rebecca Foulger commented on gene: NPRL2: NPRL2 re-reviewed for curation of GMS epilepsy panel: Sufficient cases for inclusion but variants in unaffected family members (explained by the authors as incomplete penetrance). Other members of the complex, NPRL3 and DEPDC5, are Green on the panel. Since the last curation there has been a Green review by Deb Pal (Kings College London): PMID:30093711 (2019) note 3 further probands with epilepsy (including 1 with infantile spasm and unclear effect on the protein). They also note incomplete penetrance for variants in their cohort of 73 patients (covering DEPDC5 + NPRL2 + NPRL3 genes which all form the GATOR1 complex together). Awaiting clinical review for final gene rating.
Ivone Leong Added comment: Comment on list classification: NPRL3 is confirmed to be associated with Epilepsy, familial focal on OMIM but not on Gene2Phenotype. There are >3 cases (PMID: 26505888; 26285051; 27173016) of patients from unrelated families who have familial focal epilepsy with variants in NPRL3.