ET Gene, FXTAS Prevalence

Subject: ET Gene, FXTAS Prevalence

Date: 6/28/2004

E-MOVE reports from the Eight International Congress of Parkinson’s Disease and Movement Disorders, held in Rome June 14-17, 2004. Poster (P) and Page (S) numbers are from Movement Disorders 2004;19 (supplement 9)

1. Allele 2 of the Ser9Gly polymorphism in the dopamine D3 receptor gene is responsible for the most common familial form of the essential tremor disease
G Lucotte, B Funalot, P Sokoloff
P1020; S349

A polymorphism in the dopamine D3 receptor gene is found in a large proportion of familial cases of essential tremor, according to this report.

Thirty French families with familial ET were tested for the Ser9Gly genotype of the D3 receptor gene. Families were unrelated at least as far back as three generations. Allele 2 was found in 23 of 30 families, and cosegregated with disease when present. Homozygous 2-2 patients appeared to have a more severe form of the disease, suggesting a gene dosage effect.
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2. FXTAS is a Relatively Rare Cause of Tremor or Ataxia
The genetic repeat of Fragile X-related Tremor Ataxia Syndrome (FXTAS) is rare among cohorts with tremor or ataxia, according to three studies, even while misdiagnosis of FXTAS is common. E-MOVE’s original report on FXTAS is archived at http://www.mdvu.org/emove/article.asp?ID=569

The role for fragile X premutation in essential tremor and spinocerebellar ataxia: Findings from two cohorts of Italian patients
E Di Maria, M Grasso, G Abbruzzese, P Barone, P Martinelli, S Ratto, R Sciolla, S Pigullo, F Faravelli, E Bellone, F Danga-Bricarelli, F Ajmar, P Mandich
P1054, S359

Of 114 males with essential tremor, none had premutations and 4 had repeat lengths in the “gray zone” (40-55 repeats). Of 51 males with ataxia due to no other discernible genetic cause, 2 had premutations (84 and 86 repeats), and 2 had repeat lengths in the gray zone. The two males with premutations had clinical findings consistent with a diagnosis of FXTAS. Expansion of the FMR1 gene above 55 is the cause of FXTAS.

Fragile X premutation alleles in patients with sporadic cerebellar ataxia
Y Zhao, K Puong, H Law, M Wong, I Ng, E Tan
P5; S20

Of 68 cerebellar ataxia patients with no other detected genetic cause of ataxia, none had expansion of the FMR1 gene greater than 40, and none had characteristic cerebellar white matter changes. Of 100 controls, only one had a repeat length in the “gray zone” of 40-55.

Screening of a large cohort of patients with atypical parkinsonism for repeat expansions in the FMR1 gene
C Kamm, K Buerk, T Illig, E Wichmann, European Multiple System Atrophy (EMSA) Study Group, T Gasser
P1031, S352

FMR1 Repeat length was determined in 203 patients with atypical parkinsonism: 165 MSA, 35 PSP, 2 with atypical parkinsonism, and 1 with atypical parkinsonism plus dementia, as well as in 425 controls. A premutation expansion on one allele was found in 2 female MSA patients and 1 female control. Frequency of gray-zone alleles was roughly equivalent between controls and MSA patients, and slightly higher among PSP patients, although the numbers were too small for statistical significance.

Misdiagnosis of fragile X associated tremor/ataxia syndrome
MA Leehey, E Berry-Kravis, S Jacquemont, L Zhang, R Hagerman, PJ Hagerman

Medical records were reviewed for patients with definite (18 males) or probable (15 males, 6 females) FXTAS. Previous misdiagnoses, primarily by primary care physicians, included essential tremor (12), PD (9), and a wide range of other conditions, including multiple sclerosis, myasthenia gravis, and stroke.

E-MOVE Editor: Richard Robinson, NASW, WE MOVE

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