Abstract Details

Title Heterozygous Variant in DNM1L Manifesting as Tremor and Ataxia

Topic Movement Disorders

Presentation(s) P8 - Poster Session 8 (8:00 AM-9:00 AM)

Poster/Presentation
Number 3-006

Objective The DNM1L gene encodes a member of the dynamin superfamily of GTPases, Dynamin 1-Like Protein, which plays an important role in the fission of mitochondria and peroxisomes, as well as cell membrane architecture. Heterozygous mutations in DNM1L may have a dominant negative effect and have been implicated in neonatal-onset epilepsy with hypotonia and encephalopathy. Herein, we report an adult man with neonatal-onset myoclonus and tremor with ataxia whose whole exome sequencing analysis revealed a heterozygous variant in DNM1L. Preliminary assessment of mitochondrial structure is provided.

Background This 37-year-old man presented to our movement disorder clinic with a large amplitude myoclonic tremor and ataxic gait. Mild tremulousness was noted in early childhood as well as mild motoric developmental delay. Additional neurological history is notable for a generalized seizure at age 25 years with a subsequent EEG favoring primary generalized epilepsy. His family history is unknown because the patient is adopted. Whole exam sequencing analysis revealed a heterozygous variant of uncertain significance in DNM1L (p.G575_G576insFSGASG), causing an in-frame deletion of one nucleotide with insertion of 19 nucleotides after Glycine 576.

Design/Methods Phlebotomy and two skin punch biopsies were completed on the patient and an adult male control. Mononuclear cells were cultured from peripheral blood and skin punch biopsy explants were used for electron microscopy and fibroblast culture.

Results Electron microscopy of the patient’s skin revealed smaller size mitochondria with less organized cristae. Electron microscopy results will be replicated using fibroblast culture. Mononuclear cell and fibroblast cultures will also be used to determine mitochondrial function (oxidative phosphorylation) and dynamics (via using both fluorescence-based confocal microscopy).

Conclusions The protein encoded by the DNM1L gene plays a critical role in mitochondrial morphology regulation and cell membrane architecture. Preliminary evidence suggests that mutations in this gene may present with a more indolent phenotype than previously described, including tremor and ataxia.

Authors/Disclosures
Vadim Dushkin, MD (Carilion Clinic) PRESENTER	No disclosure on file
Joseph M. Ferrara, MD, F�鶹��ýӳ�� (ECU Health)	No disclosure on file
	No disclosure on file
	No disclosure on file

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