PMID- 10502593
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20220310
IS  - 0028-4793 (Print)
IS  - 0028-4793 (Linking)
VI  - 341
IP  - 14
DP  - 1999 Sep 30
TI  - Exercise intolerance due to mutations in the cytochrome b gene of mitochondrial
      DNA.
PG  - 1037-44
AB  - BACKGROUND: The mitochondrial myopathies typically affect many organ systems and 
      are associated with mutations in mitochondrial DNA (mtDNA) that are maternally
      inherited. However, there is also a sporadic form of mitochondrial myopathy in
      which exercise intolerance is the predominant symptom. We studied the biochemical
      and molecular characteristics of this sporadic myopathy. METHODS: We sequenced
      the mtDNA cytochrome b gene in blood and muscle specimens from five patients with
      severe exercise intolerance, lactic acidosis in the resting state (in four
      patients), and biochemical evidence of complex III deficiency. We compared the
      clinical and molecular features of these patients with those previously described
      in four other patients with mutations in the cytochrome b gene. RESULTS: We found
      a total of three different nonsense mutations (G15084A, G15168A, and G15723A),
      one missense mutation (G14846A), and a 24-bp deletion (from nucleotide 15498 to
      15521) in the cytochrome b gene in the five patients. Each of these mutations
      impairs the enzymatic function of the cytochrome b protein. In these patients and
      those previously described, the clinical manifestations included progressive
      exercise intolerance, proximal limb weakness, and in some cases, attacks of
      myoglobinuria. There was no maternal inheritance and there were no mutations in
      tissues other than muscle. The absence of these findings suggests that the
      disorder is due to somatic mutations in myogenic stem cells after germ-layer
      differentiation. All the point mutations involved the substitution of adenine for
      guanine, but all were in different locations. CONCLUSIONS: The sporadic form of
      mitochondrial myopathy is associated with somatic mutations in the cytochrome b
      gene of mtDNA. This myopathy is one cause of the common and often elusive
      syndrome of exercise intolerance.
FAU - Andreu, A L
AU  - Andreu AL
AD  - H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related
      Diseases, Department of Neurology, Columbia College of Physicians and Surgeons,
      New York, NY 10032, USA.
FAU - Hanna, M G
AU  - Hanna MG
FAU - Reichmann, H
AU  - Reichmann H
FAU - Bruno, C
AU  - Bruno C
FAU - Penn, A S
AU  - Penn AS
FAU - Tanji, K
AU  - Tanji K
FAU - Pallotti, F
AU  - Pallotti F
FAU - Iwata, S
AU  - Iwata S
FAU - Bonilla, E
AU  - Bonilla E
FAU - Lach, B
AU  - Lach B
FAU - Morgan-Hughes, J
AU  - Morgan-Hughes J
FAU - DiMauro, S
AU  - DiMauro S
LA  - eng
GR  - NS11766/NS/NINDS NIH HHS/United States
GR  - P01HD32062/HD/NICHD NIH HHS/United States
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Cytochrome b Group)
RN  - 0 (DNA, Mitochondrial)
SB  - IM
CIN - N Engl J Med. 1999 Sep 30;341(14):1077-8. PMID: 10502600
CIN - N Engl J Med. 2000 Feb 10;342(6):438-9; author reply 439-40. PMID: 10681226
CIN - N Engl J Med. 2000 Feb 10;342(6):439; author reply 439-40. PMID: 10681227
MH  - Adult
MH  - Cytochrome b Group/chemistry/*genetics
MH  - DNA, Mitochondrial/*genetics
MH  - Exercise Tolerance/*genetics
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mitochondrial Myopathies/*genetics
MH  - Muscle Fatigue/*genetics
MH  - Muscles/pathology
MH  - *Mutation
MH  - Mutation, Missense
MH  - Pain/genetics
MH  - Polymerase Chain Reaction
MH  - Sequence Deletion
EDAT- 1999/09/30 09:00
MHDA- 2000/05/20 09:00
CRDT- 1999/09/30 09:00
PHST- 1999/09/30 09:00 [pubmed]
PHST- 2000/05/20 09:00 [medline]
PHST- 1999/09/30 09:00 [entrez]
AID - 10.1056/NEJM199909303411404 [doi]
PST - ppublish
SO  - N Engl J Med. 1999 Sep 30;341(14):1037-44. doi: 10.1056/NEJM199909303411404.