Pure exercise intolerance and ophthalmoplegia associated with the m.12,294G > A mutation in the MT-TL2 gene: a case report
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Pure exercise intolerance and ophthalmoplegia associated with the m.12,294G > A mutation in the MT-TL2 gene : a case report. / Soldath, Patrick; Madsen, Karen Lindhardt; Buch, Astrid Emilie; Duno, Morten; Wibrand, Flemming; Vissing, John.
I: BMC Musculoskeletal Disorders, Bind 18, 419, 10.2017.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Pure exercise intolerance and ophthalmoplegia associated with the m.12,294G > A mutation in the MT-TL2 gene
T2 - a case report
AU - Soldath, Patrick
AU - Madsen, Karen Lindhardt
AU - Buch, Astrid Emilie
AU - Duno, Morten
AU - Wibrand, Flemming
AU - Vissing, John
PY - 2017/10
Y1 - 2017/10
N2 - BACKGROUND: Pure exercise intolerance associated with exclusive affection of skeletal muscle is a very rare phenotype of patients with mitochondrial myopathy. Moreover, the exercise intolerance in these rare patients is yet not well explored, as most of known cases have not been assessed by objective testing, but only by interview. We report a patient with a mitochondrial DNA (mtDNA) mutation that gives rise to an exclusive myopathy associated with exercise intolerance and ophthalmoplegia. We quantified the patient's exercise intolerance through detailed exercise testing.CASE PRESENTATION: A 39-year-old man presented with exercise intolerance and chronic progressive external ophthalmoplegia. Sequencing of the entire mtDNA identified a m.12,294G > A mutation in the MT-TL2 gene. The mutation was heteroplasmic in skeletal muscle (75%) while undetectable in blood, urinary sediment, and buccal mucosa as well as in tissues from the patient's mother. The mutation affected a highly conserved site in the anticodon stem of the mitochondrial transfer RNA Leucine (CUN) molecule and lead to a severe combined respiratory chain defect. Exercise physiological studies in the patient demonstrated a significantly reduced maximal oxygen uptake of 20.4 ml O2 × min-1 × kg-1 (about half of normal) as well as threefold elevated lactate/pyruvate ratios.CONCLUSION: The findings of our study support that the m.12,294G > A mutation is pathogenic. Likely, the mutation arose sporadically in early embryogenesis after differentiation of the mesoderm into muscle progenitor cells, leading to a pure myopathic phenotype.
AB - BACKGROUND: Pure exercise intolerance associated with exclusive affection of skeletal muscle is a very rare phenotype of patients with mitochondrial myopathy. Moreover, the exercise intolerance in these rare patients is yet not well explored, as most of known cases have not been assessed by objective testing, but only by interview. We report a patient with a mitochondrial DNA (mtDNA) mutation that gives rise to an exclusive myopathy associated with exercise intolerance and ophthalmoplegia. We quantified the patient's exercise intolerance through detailed exercise testing.CASE PRESENTATION: A 39-year-old man presented with exercise intolerance and chronic progressive external ophthalmoplegia. Sequencing of the entire mtDNA identified a m.12,294G > A mutation in the MT-TL2 gene. The mutation was heteroplasmic in skeletal muscle (75%) while undetectable in blood, urinary sediment, and buccal mucosa as well as in tissues from the patient's mother. The mutation affected a highly conserved site in the anticodon stem of the mitochondrial transfer RNA Leucine (CUN) molecule and lead to a severe combined respiratory chain defect. Exercise physiological studies in the patient demonstrated a significantly reduced maximal oxygen uptake of 20.4 ml O2 × min-1 × kg-1 (about half of normal) as well as threefold elevated lactate/pyruvate ratios.CONCLUSION: The findings of our study support that the m.12,294G > A mutation is pathogenic. Likely, the mutation arose sporadically in early embryogenesis after differentiation of the mesoderm into muscle progenitor cells, leading to a pure myopathic phenotype.
KW - Journal Article
U2 - 10.1186/s12891-017-1781-0
DO - 10.1186/s12891-017-1781-0
M3 - Journal article
C2 - 29052516
VL - 18
JO - B M C Musculoskeletal Disorders
JF - B M C Musculoskeletal Disorders
SN - 1471-2474
M1 - 419
ER -
ID: 186188467