DO: 0111429;
Cytogenetic location: 2p25-p22 Genomic coordinates (GRCh38): 2:1-41,500,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 2p25-p22 | Essential tremor, hereditary, 2 | 602134 | Autosomal dominant | 2 |
For a phenotypic description and a discussion of genetic heterogeneity of essential tremor, see ETM1 (190300).
Higgins et al. (1997) reported linkage of an essential tremor locus on chromosome 2 in a large American family of Czech descent with dominantly inherited 'pure' essential tremor. They symbolized the locus ETM; it is also referred to as ETM2. A maximum lod score of 5.92 was obtained for the locus D2S272 located at 2p25-p22. Obligate recombinant events placed the ETM2 gene in a 15-cM candidate interval between the genetic loci D2S168 and D2S224. In the assessment of tremor in the family studies, Higgins et al. (1997) had the subjects hold their arms in a wing-beating position (with the elbows partially flexed and the shoulders abducted in the horizontal plane). Tremor amplitude was assessed by visual inspection and classified as fine, moderate, or coarse. Without presenting the data in detail, Higgins et al. (1997) suggested that the family showed anticipation. Higgins et al. (1998) found evidence for linkage to 2p in 3 other unrelated American families. Multipoint linkage analysis in all 4 American families suggested a minimal critical region of 2.18 cM between loci D2S2150 and D2S220. They also excluded linkage to the ETM1 locus on chromosome 3. The age at disease onset was 32 years +/- 18 (SD). Anticipation was not well borne out by the new families.
Higgins et al. (2003) stated that the ETM2 gene maps to 2p24.1. They identified 3 unreported dinucleotide polymorphic sites on a physical map of the ETM2 interval in a region of no recombination. A haplotype formed by 2 of these sites occurred with a frequency of 29% in 45 white cases and 9% in a sample of 35 white newborns (P less than 0.0001). The haplotype was not found in 35 normal individuals older than 60 years without tremor (P = 0.0063). This study provided evidence that an ancestral haplotype on chromosome 2p24.1 segregates with the essential tremor disease phenotype in individuals with a family history of the disorder.
Using BAC clone analysis, Higgins et al. (2004) constructed an integrated physical map of the ETM2 region on chromosome 2p24.3-p24.2.
Although Higgins et al. (2005) reported an association between essential tremor and a substitution in the HS1BP3 gene (609359), Deng et al. (2005) found no association between the same substitution and essential tremor or Parkinson disease (168600) among 222 and 285 affected patients, respectively. Furthermore, the substitution allele was present in 12 (9.1%) of 132 control individuals, indicating it is a polymorphism.
Deng, H., Le, W. D., Guo, Y., Huang, M. S., Xie, W. J., Jankovic, J. Extended study of A265G variant of HS1BP3 in essential tremor and Parkinson disease. Neurology 65: 651-652, 2005. [PubMed: 16116142] [Full Text: https://doi.org/10.1212/01.wnl.0000173033.32535.23]
Higgins, J. J., Jankovic, J., Lombardi, R. Q., Pucilowska, J., Tan, E. K., Ashizawa, T., Ruszczyk, M. U. Haplotype analysis of the ETM2 locus in familial essential tremor. Neurogenetics 4: 185-189, 2003. [PubMed: 12761658] [Full Text: https://doi.org/10.1007/s10048-003-0151-2]
Higgins, J. J., Lombardi, R. Q., Pucilowska, J., Jankovic, J., Tan, E. K., Rooney, J. P. A variant in the HS1-BP3 gene is associated with familial essential tremor. Neurology 64: 417-421, 2005. [PubMed: 15699368] [Full Text: https://doi.org/10.1212/01.WNL.0000153481.30222.38]
Higgins, J. J., Lombardi, R. Q., Pucilowska, J., Ruszczyk, M. U. Integrated physical map of the human essential tremor gene region (ETM2) on chromosome 2p24.3-p24.2 Am. J. Med. Genet. 127B: 128-130, 2004. [PubMed: 15108195] [Full Text: https://doi.org/10.1002/ajmg.b.20152]
Higgins, J. J., Loveless, J. M., Jankovic, J., Patel, P. I. Evidence that a gene for essential tremor maps to chromosome 2p in four families. Mov. Disord. 13: 972-977, 1998. Note: Erratum: Mov. Disord. 14: 200 only, 1999. [PubMed: 9827627] [Full Text: https://doi.org/10.1002/mds.870130621]
Higgins, J. J., Pho, L. T., Nee, L. E. A gene (ETM) for essential tremor maps to chromosome 2p22-p25. Mov. Disord. 12: 859-864, 1997. [PubMed: 9399207] [Full Text: https://doi.org/10.1002/mds.870120605]