LGI1

Inheritance Pattern: AD

Disease ID:MONDO:0700090

Submitter: Labcorp Genetics (formerly Invitae)

Inheritance Pattern: AD

Disease ID:MONDO:0010898

Submitter: Orphanet

Inheritance Pattern: AD

Disease ID:MONDO:0010898

Submitter: PanelApp Australia

Inheritance Pattern: AD

Disease ID:MONDO:0010898

Submitter: ClinGen

Autosomal Dominant Epilepsy with Auditory Features (ADEAF), also known as familial temporal lobe epilepsy, is characterized by seizures originating in the temporal lobe associated with auditory symptoms (ringing, buzzing, and distortion of sounds) and receptive aphasia. The condition can also be associated with non-auditory seizures, including tonic-clonic seizures. Onset can occur from early childhood through the 5th decade, typically during adolescence or early adulthood, and seizures tend to be well-controlled. ADEAF is inherited in an autosomal dominant pattern with incomplete penetrance, estimated at approximately 60%. Rare de novo mutations have been reported and ADEAF is associated with intrafamilial variability. LGI1 is the primary gene implicated in ADEAF and was initially described in 2002 (Kalichov et al, PMID 11810107). Since that time, numerous families have been reported in the literature, with over 40 disease-causing mutations reported, typically unique to individual families. The mutation spectrum includes nonsense, frameshift, splice site, missense and large deletions with loss of function as the mechanism of disease (Kalichov et al, PMID 11810107; Morante-Redolat et al, PMID 11978770; Chabrol et al, PMID 17296837; Sadleir et al, PMID: 24206907; Hedera et al, PubMed 15009222; Michelucci et al, PMID 14510822; Fanciulli et al, PMID 22496201; Kesim et al, PMID 26773249). Supporting experimental evidence includes functional alteration in non-patient cells (Yokoi et al, PMID 25485908), expression (Fukata et al, PMID 16990550; Fukata et al, 20133599), non-human model organism (Yu et al, 20130004; Baulac et al, 22589250; Teng et al, 20819949; Chabrol et al, 20659958; Fukata et al, 20133599), and rescue in non-human model organism (Fukata et al, 20133599). A genetic evidence score of 12 and experimental evidence score of 6 results in a total score of 18. Evidence supporting an association between LGI1 and ADEAF has been replicated over time; therefore, the gene-disease validity has been classified as DEFINITIVE.