Abstract Details

Title Exome Sequencing Identifies a Novel PRPS1 Mutation and a Novel DNM2 Mutation

Topic Peripheral Nerve

Presentation(s) (-)

Poster/Presentation
Number 003

Objective

Background Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is known to cause X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), which is characterized by peripheral neuropathy, sensorineural hearing loss, and optic neuropathy. PRPS1 affects first step of nucleotides synthesis in ubiquitous human tissues including cochlea. Dynamin-2 (DNM2) gene is involved in several cellular processes, such as endocytotic pathways, vesicle trafficking and microtubular dynamics. DNM2 mutations are associated with autosomal dominant centronuclear myopathy (CNM), dominant intermediate (CMTDIB) and axonal Charcot-Marie-Tooth disease type 2M (CMT2M).

Design/Methods We enrolled two male patients from two unrelated CMT families to perform whole exom study and subsequent sequencing.

Results Case1. A 16-year-old male with early onset sensorinueral hearing loss noticed gating disturbance due to weakness of distal lower limbs at 4 year of age. Two relatives on the maternal side had same manifestations started at 4-5 year of age. He complained neither cognitive dysfunction nor vocal dysfunction, diaphragmatic paralysis. A novel c.362C>G (Ala121Gly) mutation in PRPS1 gene was detected, and co-segregated in this family. Case2. A 62-year-old male presented gait disturbance and dysarthria. At 18 years old, he noticed progressive dysarthria as well as walking difficulty. Electrophysiological studies showed an axonal neuropathy with neurogenic action potentials. Exome sequencing was performed and revealed a novel c.839C>T (Thr280Met) mutation in the DNM2 gene. These mutations of two cases were not found in 200 control samples and located on the well conserved.

Conclusions In this study, we found a novel PRPS1 mutation in CMTX5 patient and novel DNM2 mutation in CMT2M patient. Whole exome study and subsequent capillary sequencing is efficient tool for detecting very rare types of CMT patients, and we suggest that this study contribute to expend phenotypic spectrum of CMT.

Authors/Disclosures
Jin Park, MD (Ewha Womans Univ Mokdong Hospital) PRESENTER	Dr. Park has nothing to disclose.
Jae Won Hyun, MD	No disclosure on file
Hwa Kyoung Chung, MD	No disclosure on file
	No disclosure on file
Dara G. Jamieson, MD	Dr. Jamieson has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Jamieson has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Medico-legal. Dr. Jamieson has received publishing royalties from a publication relating to health care. Dr. Jamieson has received personal compensation in the range of $100,000-$499,999 for serving as a Expert, Consultant with Health and Human Services, Department of Justice.
Kyoung-Gyu Choi (Ewha Womans Univ Hospital)	No disclosure on file
Byung-Ok Choi, MD, PhD (Ewha Womans University)	No disclosure on file

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