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A step toward essential tremor gene discovery: identification of extreme phenotype and screening of HTRA2 and ANO3

View Article: PubMed Central - PubMed

ABSTRACT

Background: Essential tremor (ET) is characterized by a frequent family history. No monogenic form of ET has been identified. We aimed at exploring ET patients to identify distinct subgroups and facilitate the identification of ET genes. We tested for the presence of HTRA2 p.G399S, and ANO3 p. W490C, p. R484 W and p. S685G mutations.

Methods: Between June 2011 and November 2013, all consecutive patients suspected with ET were prospectively included in a prospective, monocentric study. Family history, age at onset (AAO), features of tremor, benefit of alcohol and drugs, electrophysiological recording findings were collected. Sanger sequencing was performed for HTRA2 and ANO3 mutations screening.

Results: Sixty eight patients were investigated. Fourteen diagnosed with psychogenic (5) or dystonic tremor (9) were excluded. Regarding the 54 ET patients, mean AAO was 48 years (6–77), and mean disease duration 15 years (1–55). Bimodal distribution of AAO was consistent with phenotypic subgroups. In patients with AAO before 30 years, marked benefit of alcohol (p < 0.01) and ET family history (p < 0.01) were more frequent and the disease progression less severe (p < 0.0001). Neither HTRA2 nor ANO3 mutation were identified in our patients.

Conclusions: Our data support that distinct ET phenotypic subgroups may be encountered. We recommend to study separately extreme phenotypes of ET, particularly autosomal dominant families with early AAO (<30 years) and marked benefit of alcohol, to facilitate the identification of ET genes. Electromyographic recording remains a support to distinguish ET from differential diagnosis. HTRA2 and ANO3 mutations are not common causes of ET.

No MeSH data available.


Related in: MedlinePlus

Bimodal distribution of age at onset of tremor
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Fig1: Bimodal distribution of age at onset of tremor

Mentions: The main clinical and electrophysiological data of the remaining 54 patients are summarized in Tables 1 and 2 and in Fig. 1.Table 1


A step toward essential tremor gene discovery: identification of extreme phenotype and screening of HTRA2 and ANO3
Bimodal distribution of age at onset of tremor
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5120508&req=5

Fig1: Bimodal distribution of age at onset of tremor
Mentions: The main clinical and electrophysiological data of the remaining 54 patients are summarized in Tables 1 and 2 and in Fig. 1.Table 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: Essential tremor (ET) is characterized by a frequent family history. No monogenic form of ET has been identified. We aimed at exploring ET patients to identify distinct subgroups and facilitate the identification of ET genes. We tested for the presence of HTRA2 p.G399S, and ANO3 p. W490C, p. R484 W and p. S685G mutations.

Methods: Between June 2011 and November 2013, all consecutive patients suspected with ET were prospectively included in a prospective, monocentric study. Family history, age at onset (AAO), features of tremor, benefit of alcohol and drugs, electrophysiological recording findings were collected. Sanger sequencing was performed for HTRA2 and ANO3 mutations screening.

Results: Sixty eight patients were investigated. Fourteen diagnosed with psychogenic (5) or dystonic tremor (9) were excluded. Regarding the 54 ET patients, mean AAO was 48 years (6–77), and mean disease duration 15 years (1–55). Bimodal distribution of AAO was consistent with phenotypic subgroups. In patients with AAO before 30 years, marked benefit of alcohol (p < 0.01) and ET family history (p < 0.01) were more frequent and the disease progression less severe (p < 0.0001). Neither HTRA2 nor ANO3 mutation were identified in our patients.

Conclusions: Our data support that distinct ET phenotypic subgroups may be encountered. We recommend to study separately extreme phenotypes of ET, particularly autosomal dominant families with early AAO (<30 years) and marked benefit of alcohol, to facilitate the identification of ET genes. Electromyographic recording remains a support to distinguish ET from differential diagnosis. HTRA2 and ANO3 mutations are not common causes of ET.

No MeSH data available.


Related in: MedlinePlus