ORPHA: 101046; DO: 0060751;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 7q22.1 | {Epilepsy, familial temporal lobe, 7} | 616436 | Autosomal dominant | 3 | RELN | 600514 |
A number sign (#) is used with this entry because of evidence that familial temporal lobe epilepsy-7 (ETL7) is caused by heterozygous mutation in the RELN gene (600514) on chromosome 7q22.
Familial temporal lobe epilepsy-7 (ETL7) is a form of autosomal dominant lateral temporal lobe epilepsy characterized by focal seizures with prominent auditory symptoms (summary by Dazzo et al., 2015).
For a general description and a discussion of genetic heterogeneity of familial temporal lobe epilepsy, see ETL1 (600512).
Dazzo et al. (2015) reported 7 unrelated families with autosomal dominant lateral temporal lobe epilepsy. Affected individuals had focal epilepsy with auras consistent with a lateral temporal origin; auras were mainly auditory and manifest as ringing, humming, sounds, voices, or music. Some patients had receptive-aphasic symptoms. No structural insults to the temporal region were detected.
The transmission pattern of ETL7 in the families reported by Dazzo et al. (2015) was consistent with autosomal dominant inheritance with incomplete penetrance.
In 7 unrelated families of Italian descent with ETL7, Dazzo et al. (2015) identified 7 different heterozygous missense mutations in the RELN gene (see, e.g., 600514.0003-600514.0006). Mutations in the LGI1 gene (604619) had been excluded in these families. RELN mutations in the first 4 families were found by whole-exome sequencing; mutations in the 3 subsequent families were found by parallel sequencing of RELN exons in 11 small families with the disorder. Functional studies of the variants were not performed, but 3-dimensional modeling predicted that the mutations would result in structural defects and protein misfolding, which could lead to degradation of the altered proteins. Affected individuals from 4 families had reduced (up to 50%) serum levels of the main 310-kD reelin isoform compared to controls, which most likely resulted from impaired secretion of the altered proteins from hepatocytes. These findings suggested that the mutations resulted in a loss of function. Overall, RELN mutations occurred in 7 (17.5%) of 40 families studied; mutations were not found in families with mesial temporal lobe epilepsy, suggesting that RELN mutations may specifically cause lateral temporal lobe epilepsy.
Dazzo, E., Fanciulli, M., Serioli, E., Minervini, G., Pulitano, P., Binelli, S., Di Bonaventura, C., Luisi, C., Pasini, E., Striano, S., Striano, P., Coppola, G., and 11 others. Heterozygous reelin mutations cause autosomal-dominant lateral temporal epilepsy. Am. J. Hum. Genet. 96: 992-1000, 2015. [PubMed: 26046367] [Full Text: https://doi.org/10.1016/j.ajhg.2015.04.020]