Epilepsy, Familial Adult Myoclonic, 3 (MARCHF6)
| Dred_ID | RD00060 |
| OMIM ID | 613608 |
| Disease name | Epilepsy, Familial Adult Myoclonic, 3 |
| Alternative names | FAME3 |
| Category | Genetic diseases, Rare diseases, Metabolic diseases |
| Phenotype | OMIM: Familial adult myoclonic epilepsy-3 (FAME3) is an autosomal dominant neurologic disorder characterized by onset of cortical tremor, mainly affecting the hands and voice, between 10 and 40 years of age, with adult onset being more common. Most affected individuals develop epilepsy with generalized tonic-clonic seizures; some may have partial or absence seizures. The disorder is nonprogressive or slowly progressive, and most patients respond to antiseizure medication (summary by Florian et al., 2019). For a phenotypic description and a discussion of genetic heterogeneity of familial adult myoclonic epilepsy, see FAME1 (601068). MalaCards based summary: Epilepsy, Familial Adult Myoclonic, 3, also known as fcmte3, is related to epilepsy, familial adult myoclonic, 2 and familial adult myoclonic epilepsy. An important gene associated with Epilepsy, Familial Adult Myoclonic, 3 is FAME3 (Epilepsy, Familial Adult Myoclonic, 3), and among its related pathways/superpathways is Tryptophan metabolism. Related phenotypes are tremor and myoclonus. |
| Miscellaneouse | adult onset childhood onset has been reported movements ('tremors') characterized by 8 to 10-hz discharges nonprogressive course tremor may be elicited by movement or postural maintenance anticonvulsants are effective (phenobarbital, valproic acid, benzodiazepines) tremor is aggravated by low glucose or light |
| Prevalence | an estimated prevalence of 1/35,000 was reported in Japan [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | MARCHF6 |
| Alias symbols | TEB4; DOA10; FAME3; MARCH6; RNF176; MARCH-VI |
| Gene name | membrane associated ring-CH-type finger 6 |
| Gene map locus | 5p15.2; chr5:10,353,693-10,440,388(+) |
| Ensembl Gene ID | ENSG00000145495 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | This gene encodes a member of a family of membrane-associated E3 ubiquitin ligases containing RING-CH-type zinc finger motifs. Ubiquitination of type II deiodinase by the encoded protein is an important regulatory step in thyroid hormone signalling. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. |
| Repeat unit | TTTCA/TTTTA |
| Normal repeat copies | 10-30(TTTTA) |
| Pathogenic repeat copies | ≥660 |
| Gene | MARCHF6 |
| Repeat location | intron |
| Chromosome locus | chr5:10356345-10356410 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | These somatic expansions were associated with genomic microrearrangements, with larger expansions associated with more microrearrangements. There was also an inverse correlation between TTTCA expansion size and age at epilepsy onset in patients. Patient cells did not show any difference in MARCHF6 RNA or protein expression compared to those of controls, and there was no difference in the level of intron 1-containing RNA, thus excluding a massive accumulation of abnormally spliced mRNA carrying the expansion in these cells. |
| Pathway annotation | Reactome, KEGG |
| PMID | 31664039 |
| Authors | Rahel T Florian, Florian Kraft, Elsa Leitão, Sabine Kaya, Stephan Klebe, Eloi Magnin, et al |
| Title | Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3 |
| Journal | Nature communication |
| Year | 2019 |