Alternative titles; symbols
DO: 0111694;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 4q32.1 | ?Epilepsy, familial adult myoclonic, 7 | 618075 | Autosomal dominant | 3 | RAPGEF2 | 609530 |
A number sign (#) is used with this entry because of evidence that familial adult myoclonic epilepsy-7 (FAME7) is caused by a heterozygous 5-bp repeat expansion (TTTCA(n)) in the RAPGEF2 gene (609530) on chromosome 4q32. One such patient has been reported.
For a phenotypic description and a discussion of genetic heterogeneity of familial adult myoclonic epilepsy, see FAME1 (601068).
Ishiura et al. (2018) reported a small Japanese family (F8241) with familial adult myoclonic epilepsy. Clinical details were limited. The male proband showed myoclonic tremor from the age of 18 years. He had a seizure at age 27, when anitconvulsants and beta-blocker were started. No brain MRI abnormalities or giant somatosensory evoked potentials were observed. The proband's mother was unaffected, his father reportedly had tremulous movements, and his deceased paternal uncle was affected. DNA was not available from the father or paternal uncle.
The transmission pattern of FAME7 in the family reported by Ishiura et al. (2018) was consistent with autosomal dominant inheritance.
In a Japanese patient (F8241) with FAME7, Ishiura et al. (2018) identified a heterozygous 5-bp TTTCA(n) repeat in intron 14 of the RAPGEF2 gene (609530.0001). This expansion was located between two 5-bp TTTTA(n) repeats. TTTCA(n) repeat expansions were not found in the reference sequence or in 1,000 control individuals. TTTTA(n) expanded repeats were found in 0.5% of controls, suggesting that the TTTCA(n) expansion is responsible for the phenotype. The mutation was found by searching for repeat motifs using data from whole-genome sequence analysis and Southern blot analysis after a similar repeat expansion was identified in the SAMD12 gene (618073) in patients with FAME1. Functional studies of the RAPGEF2 variant and studies of patient cells were not performed, but based on studies with SAMD12, Ishiura et al. (2018) postulated that the expression of RNA molecules containing expansions of UUUCA and UUUUA repeats per se is involved in the pathogenesis of the disorder, rather than altered physiologic function of each individual gene.
Ishiura, H., Doi, K., Mitsui, J., Yoshimura, J., Matsukawa, M. K., Fujiyama, A., Toyoshima, Y., Kakita, A., Takahashi, H., Suzuki, Y., Sugano, S., Qu, W., and 55 others. Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy. Nature Genet. 50: 581-590, 2018. [PubMed: 29507423] [Full Text: https://doi.org/10.1038/s41588-018-0067-2]