Abstract
We studied 22 subjects carrying the A3243G point mutation of human mitochondrial DNA (mtDNA). In 14 cases the clinical phenotype was characterized by mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), while 8 patients had chronic progressive external ophthalmoplegia (CPEO). The proportion of A3243G heteroplasmy in muscle was determined by two methods: densitometry on a diagnostic restriction-fragment length polymorphism and solid-phase mini-sequencing. We found a highly significant inverse correlation between the percentage of A3243G mutation and the specific activity of complex 1, the respiratory complex with the highest number of mtDNA-encoded subunits, suggesting a direct effect of the mutation on mtDNA translation. No correlation was observed between the percentage of mutated mtDNA and the presence or absence of specific clinical features, such as stroke, ophthalmoplegia and diabetes mellitus. However, in the MELAS group the percentage of mutated mtDNA molecules was strongly correlated with the age of onset, while no such correlation was found in the CPEO group, suggesting a different time-dependent evolution of the mutation in the two groups. Finally, in contrast with other mtDNA mutations associated with ragged-red fibres (RRF), in both MELAS3243 and CPE03243 we observed a high proportion of RRF that were positive to the histochemical reaction to cytochrome c oxidase, a morphological feature that seems to be specific for the neuromuscular phenotypes associated with mutations affecting the tRNALeu(UUR) gene.
| Original language | English |
|---|---|
| Pages (from-to) | 304-312 |
| Number of pages | 9 |
| Journal | Journal of Neurology |
| Volume | 242 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 1995 |
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Keywords
- Chronic progressive external ophthalmoplegia
- Lactic acidosis
- Mitochondrial encephalomyopathy
- Ragged-red fibres
- Stroke-like episodes
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
Cite this
Genotype to phenotype correlations in mitochondrial encephalomyopathies associated with the A3243G mutation of mitochondrial DNA. / Mariotti, Caterina; Savarese, Nicola; Suomalainen, Anu; Rimoldi, Marco; Comi, Giacomo; Prelle, Alessandro; Antozzi, Carlo; Servidei, Serena; Jarre, Laura; DiDonato, Stefano; Zeviani, Massimo.
In: Journal of Neurology, Vol. 242, No. 5, 05.1995, p. 304-312.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genotype to phenotype correlations in mitochondrial encephalomyopathies associated with the A3243G mutation of mitochondrial DNA
AU - Mariotti, Caterina
AU - Savarese, Nicola
AU - Suomalainen, Anu
AU - Rimoldi, Marco
AU - Comi, Giacomo
AU - Prelle, Alessandro
AU - Antozzi, Carlo
AU - Servidei, Serena
AU - Jarre, Laura
AU - DiDonato, Stefano
AU - Zeviani, Massimo
PY - 1995/5
Y1 - 1995/5
N2 - We studied 22 subjects carrying the A3243G point mutation of human mitochondrial DNA (mtDNA). In 14 cases the clinical phenotype was characterized by mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), while 8 patients had chronic progressive external ophthalmoplegia (CPEO). The proportion of A3243G heteroplasmy in muscle was determined by two methods: densitometry on a diagnostic restriction-fragment length polymorphism and solid-phase mini-sequencing. We found a highly significant inverse correlation between the percentage of A3243G mutation and the specific activity of complex 1, the respiratory complex with the highest number of mtDNA-encoded subunits, suggesting a direct effect of the mutation on mtDNA translation. No correlation was observed between the percentage of mutated mtDNA and the presence or absence of specific clinical features, such as stroke, ophthalmoplegia and diabetes mellitus. However, in the MELAS group the percentage of mutated mtDNA molecules was strongly correlated with the age of onset, while no such correlation was found in the CPEO group, suggesting a different time-dependent evolution of the mutation in the two groups. Finally, in contrast with other mtDNA mutations associated with ragged-red fibres (RRF), in both MELAS3243 and CPE03243 we observed a high proportion of RRF that were positive to the histochemical reaction to cytochrome c oxidase, a morphological feature that seems to be specific for the neuromuscular phenotypes associated with mutations affecting the tRNALeu(UUR) gene.
AB - We studied 22 subjects carrying the A3243G point mutation of human mitochondrial DNA (mtDNA). In 14 cases the clinical phenotype was characterized by mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), while 8 patients had chronic progressive external ophthalmoplegia (CPEO). The proportion of A3243G heteroplasmy in muscle was determined by two methods: densitometry on a diagnostic restriction-fragment length polymorphism and solid-phase mini-sequencing. We found a highly significant inverse correlation between the percentage of A3243G mutation and the specific activity of complex 1, the respiratory complex with the highest number of mtDNA-encoded subunits, suggesting a direct effect of the mutation on mtDNA translation. No correlation was observed between the percentage of mutated mtDNA and the presence or absence of specific clinical features, such as stroke, ophthalmoplegia and diabetes mellitus. However, in the MELAS group the percentage of mutated mtDNA molecules was strongly correlated with the age of onset, while no such correlation was found in the CPEO group, suggesting a different time-dependent evolution of the mutation in the two groups. Finally, in contrast with other mtDNA mutations associated with ragged-red fibres (RRF), in both MELAS3243 and CPE03243 we observed a high proportion of RRF that were positive to the histochemical reaction to cytochrome c oxidase, a morphological feature that seems to be specific for the neuromuscular phenotypes associated with mutations affecting the tRNALeu(UUR) gene.
KW - Chronic progressive external ophthalmoplegia
KW - Lactic acidosis
KW - Mitochondrial encephalomyopathy
KW - Ragged-red fibres
KW - Stroke-like episodes
UR - http://www.scopus.com/inward/record.url?scp=0029032410&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029032410&partnerID=8YFLogxK
U2 - 10.1007/BF00878873
DO - 10.1007/BF00878873
M3 - Article
C2 - 7643139
AN - SCOPUS:0029032410
VL - 242
SP - 304
EP - 312
JO - Journal of Neurology
JF - Journal of Neurology
SN - 0340-5354
IS - 5
ER -