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Abstract Details

Mitochondrial DNA (mtDNA) Multiple Deletions: mtDNA Analysis by Massively Parallel Sequencing
Muscle Disease/Neuromuscular Junction
P07 - (-)
020
BACKGROUND: The molecular diagnosis of many patients with mitochondrial disorder remains elusive. Defects in the mtDNA can be easily detected by the recently developed one-step comprehensive massively parallel sequencing (LR-PCR/MPS) based analysis for simultaneous detection of mtDNA point mutations and large mtDNA deletions with heteroplasmy quantification.
DESIGN/METHODS: We tested muscle of 2 groups of patients, age 21-72 years, by LR-PCR/MPS. Group #1 included 11 patients with myopathy alone or associated with progressive external ophthalmoplegia and/or peripheral neuropathy, 10 of whom had histological evidence for mitochondrial myopathy. Group #2 included 7 patients with central and peripheral nervous system involvement, 4 with mitochondrial myopathy on biopsy and 3 with normal muscle biopsy. Two patients from group #1 and 4 patients from group #2 had negative mtDNA common point mutations and deletion screening by traditional PCR/ASO and Southern blot, respectively.
RESULTS: Group #1: All 11 patients showed multiple mtDNA deletions; in addition, 3 patients carried a primary pathogenic mtDNA mutation. Group #2: 3 patients had multiple mtDNA deletions and 2 of them, age 38, carried also pathogenic mtDNA missense mutations; 2 patients harbored pathogenic mtDNA missense mutations associated with a large scale deletion in one; 2 subjects (age 32 and 55 years, respectively) showed normal mtDNA.
CONCLUSIONS: Histological signs of mitochondrial myopathy are likely to be accompanied by mtDNA deletions or point mutations. While the etiology of multiple deletions is indeterminate and requires nuclear genes analysis, mtDNA deletions accompanying pathogenic point mutations, independently from patient's age, may contribute to the phenotypic severity. The increased sensitivity of LR-PCR/MPS might decrease specificity of the mtDNA deletions as finding suggestive of defects in nuclear genes affecting mtDNA maintenance.
Authors/Disclosures
Margherita Milone, MD, FAAN (Mayo Clinic)
PRESENTER 		Dr. Milone has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cartesian Therapeutics. Dr. Milone has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Genetics, AAN. The institution of Dr. Milone has received research support from Mayo Clinic, CCaTS-CBD. The institution of Dr. Milone has received research support from Mayo Clinic, SGP Award. The institution of Dr. Milone has received research support from MDA for Care Center grant. The institution of Dr. Milone has received research support from Regenerative medicine Minnesota.
Lee-jun C. Wong, PhD (Baylor College of Medicine) No disclosure on file
No disclosure on file
Matthew S. Robbins, MD, FAAN (Weill Cornell Medicine) Dr. Robbins has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Robbins has received publishing royalties from a publication relating to health care. Dr. Robbins has a non-compensated relationship as a Board of Directors member, 好色先生 Program speaker with American Headache Society that is relevant to AAN interests or activities. Dr. Robbins has a non-compensated relationship as a Board of Directors member, 好色先生 Program speaker with New York State Neurological Society that is relevant to AAN interests or activities. Dr. Robbins has a non-compensated relationship as a Editorial Board Member with Continuum, 好色先生 that is relevant to AAN interests or activities.
Walter N. Folger, MD, FAAN (Mayo Clinic) No disclosure on file
Brian G. Weinshenker, MD, FAAN (University of Virginia Health System) Dr. Weinshenker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CANbridge Pharmaceuticals. Dr. Weinshenker has received personal compensation in the range of $0-$499 for serving as a Consultant for CALIBR. Dr. Weinshenker has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Group (Chugai, Genentech, Roche). Dr. Weinshenker has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharmaceuticals. Dr. Weinshenker has received research support from Guthy Jackson Charitable Foundation. Dr. Weinshenker has received intellectual property interests from a discovery or technology relating to health care.