Abstract Details

Title The Clinical Spectrum of ANO3—Report of a New Family and Literature Review

Topic Movement Disorders

Presentation(s) P1 - Poster Session 1 (8:00 AM-9:00 AM)

Poster/Presentation
Number 3-016

Objective To describe the clinical and genetic findings of a new ANO3 family, and to attempt a genotype-phenotype correlation reviewing all previous published cases of ANO3.

Background Mutations in ANO3 are a rare cause of autosomal dominant isolated or combined dystonia, mainly presenting in adulthood.

Design/Methods Written informed consent was obtained from all patients. Demographic and clinical data were collected from medical records. A NGS panel including genes associated with dystonia was performed. The terms “ANO3”, “TMEM16C”, “anoctamin 3”, “anoctamin-3”, “DYT-24”, and “DYT-ANO3” were searched in the online database PubMed.

Results We extensively characterize a new, large ANO3 family with six affected carriers. The proband is a young girl who had suffered from tremor and painful dystonic movements in her right arm since the age of 11 years. She later developed a diffuse dystonic tremor and mild extrapyramidal signs (i.e., rigidity and hypodiadochokinesis) in her right arm. She also suffered from psychomotor delay and learning difficulties. Repeated structural and functional neuroimaging were unremarkable. A dystonic tremor was also present in her two sisters. Her paternal aunt, father, and a third older sister presented episodic postural tremor in the arms. The father and one sister also presented learning difficulties. The heterozygous p.G6V variant in ANO3 was identified in all affected subjects. By reviewing the previous literature on ANO3, we were able to divide ANO3 cases into two major groups, where younger patients displayed a more severe phenotype, probably due to variants near the scrambling domain.

Conclusions We describe the phenotype of a new ANO3 family and highlight the need for functional studies to explore the impact of ANO3 variants on its phospholipid scrambling activity.

Authors/Disclosures
Marco Percetti, MD (University of Milan-Bicocca) PRESENTER	Dr. Percetti has nothing to disclose.
Michela Zini	No disclosure on file
Paola Soliveri	No disclosure on file
Filippo Cogiamanian	No disclosure on file
Mariarosa Ferrara	No disclosure on file
Eva Orunesu	No disclosure on file
Alessandra Ranghetti (ASST GAETANO-PINI CENTRO PARKINSON)	No disclosure on file
Carlo Ferrarese, MD, PhD (University of Milano-Bicocca)	Dr. Ferrarese has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI. Dr. Ferrarese has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EISAI.
Gianni Pezzoli, MD (MD)	Dr. Pezzoli has nothing to disclose.
Barbara Garavaglia	No disclosure on file
Ioannis U. Isaias, MD (University of Wurzburg)	Dr. Isaias has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Newronika. Dr. Isaias has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Dr. Isaias has stock in Newronika. Dr. Isaias has received research support from Fondazione Grigioni per il Morbo di Parkinson. The institution of Dr. Isaias has received research support from Fresco Parkinson Institute Italia Onlus. The institution of Dr. Isaias has received research support from Deutsche Forschungsgemeinschaft.
Giorgio Sacilotto (ASST-Gaetano Pini-CTO)	No disclosure on file

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